Journals
Journal:
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
ISSN:
1138-7548
Year:
2024
Vol.:
80
N°:
1
pp.
149 - 160
Bariatric surgery has become a recognized and effective procedure for treating obesity and type 2 diabetes (T2D). Our objective was to directly compare the caloric intake-independent effects of sleeve gastrectomy (SG) and single anastomosis duodenoileal bypass with SG (SADI-S) on glucose tolerance in rats with diet-induced obesity (DIO) and to elucidate the differences between bariatric surgery and caloric restriction.A total of 120 adult male Wistar rats with DIO and insulin resistance were randomly assigned to surgical (sham operation, SG, and SADI-S) and dietary (pair-feeding the amount of food eaten by animals undergoing the SG or SADI-S surgeries) interventions. Body weight and food intake were weekly monitored, and 6 weeks after interventions, fasting plasma glucose, oral glucose and insulin tolerance tests, plasma insulin, adiponectin, GIP, GLP-1, and ghrelin levels were determined.The body weight of SADI-S rats was significantly (p < 0.001) lower as compared to the sham-operated, SG, and pair-fed groups. Furthermore, SADI-S rats exhibited decreased whole body fat mass (p < 0.001), lower food efficiency rates (p < 0.001), and increased insulin sensitivity, as well as improved glucose and lipid metabolism compared to that of the SG and pair-fed rats.SADI-S was more effective than SG, or caloric restriction, in improving glycemic control and metabolic profile, with a higher remission of insulin resistance as well as long-term weight loss.
Journal:
EUROPEAN JOURNAL OF ENDOCRINOLOGY
ISSN:
0804-4643
Year:
2023
Vol.:
188
N°:
7
pp.
564 - 577
Background Growing evidence suggests the key role of ghrelin in the onset and progression of nonalcoholic fatty liver disease (NAFLD). The potential participation of ghrelin and the ghrelin receptor antagonist, LEAP-2, in the onset of liver fibrosis in patients with severe obesity and NAFLD through the regulation of TGF-& beta;1-induced hepatic stellate cell (HSC) activation was investigated. Methods Circulating (n = 179) and hepatic expression (n = 95) of ghrelin and LEAP-2 were measured in patients with severe obesity and available liver pathology analysis undergoing Roux-en-Y gastric bypass (RYGB). The effect of ghrelin isoforms and LEAP-2 on TGF-& beta;1-induced HSC activation, fibrogenic response, and contractile properties was evaluated in vitro in human LX-2 cells. Results Plasma and hepatic ghrelin were negatively associated, while LEAP-2 exhibited a positive association with liver fibrosis in patients with obesity and NAFLD. Six months after RYGB, hepatic function was improved and, although acylated ghrelin and LEAP-2 concentrations remained unchanged, both hormones were inversely related to post-surgical levels of profibrogenic factors TGF-& beta;1 and TIMP-1. Acylated ghrelin treatment reversed TGF-& beta;1-induced myofibroblast-like phenotype, collagen contractile properties, and the upregulation of factors involved in HSC activation and fibrogenesis via PI3K/Akt/mTOR pathway. Moreover, acylated ghrelin inhibited the mild HSC activation induced by LEAP-2. Conclusions Ghrelin is an anti-fibrogenic factor blocking HSC activation induced by the most potent fibrogenic cytokine, TGF-& beta;1, and LEAP-2. The imbalance between acylated ghrelin and ghrelin receptor antagonist LEAP-2 might contribute to maintain liver fibrosis in patients with obesity and NAFLD.
Journal:
FRONTIERS IN IMMUNOLOGY
ISSN:
1664-3224
Year:
2023
Vol.:
14
pp.
1138316
Authors:
Oliveras-Canellas, N.; Moreno-Navarrete, J. M.; Lorenzo, P. M.; et al.
Journal:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Year:
2023
Vol.:
109
N°:
1
pp.
e145 - e154
Context Climate change and global warming have been hypothesized to influence the increased prevalence of obesity worldwide. However, the evidence is scarce. Objective We aimed to investigate how outside temperature might affect adipose tissue physiology and metabolic traits. Methods The expression of genes involved in thermogenesis/browning and adipogenesis were evaluated (through quantitative polymerase chain reaction) in the subcutaneous adipose tissue (SAT) from 1083 individuals recruited in 5 different regions of Spain (3 in the North and 2 in the South). Plasma biochemical variables and adiponectin (enzyme-linked immunosorbent assay) were collected through standardized protocols. Mean environmental outdoor temperatures were obtained from the National Agency of Meteorology. Univariate, multivariate, and artificial intelligence analyses (Boruta algorithm) were performed. Results The SAT expression of genes associated with browning (UCP1, PRDM16, and CIDEA) and ADIPOQ were significantly and negatively associated with minimum, average, and maximum temperatures. The latter temperatures were also negatively associated with the expression of genes involved in adipogenesis (FASN, SLC2A4, and PLIN1). Decreased SAT expression of UCP1 and ADIPOQ messenger RNA and circulating adiponectin were observed with increasing temperatures in all individuals as a whole and within participants with obesity in univariate, multivariate, and artificial intelligence analyses. The differences remained statistically significant in individuals without type 2 diabetes and in samples collected during winter. Conclusion Decreased adipose tissue expression of genes involved in browning and adiponectin with increased environmental temperatures were observed. Given the North-South gradient of obesity prevalence in these same regions, the present observations could have implications for the relationship of the obesity pandemic with global warming.
Journal:
FRONTIERS IN ENDOCRINOLOGY
ISSN:
1664-2392
Year:
2023
Vol.:
14
pp.
1185456
Introduction: Obesity contributes to ectopic fat deposition in non-adipose organs, including the pancreas. Pancreas steatosis associates with inflammation and beta-cell dysfunction, contributing to the onset of insulin resistance and type 2 diabetes. An improvement of pancreatic steatosis and indices of insulin resistance is observed following bariatric surgery, but the underlying mechanisms remain unknown. We sought to analyze whether guanylin (GUCA2A) and uroguanylin (GUCA2B), two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of pancreas fat accumulation after bariatric surgery. Methods: Pancreas steatosis, inflammation, islet number and area were measured in male Wistar rats with diet-induced obesity (n=125) subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by gastrectomized animals) interventions. The tissue distribution of guanylate cyclase C (GUCY2C) and the expression of the guanylin system were evaluated in rat pancreata by real-time PCR, Western-blot and immunohistochemistry. The effect of guanylin and uroguanylin on factors involved in insulin secretion and lipogenesis was determined in vitro in RIN-m5F beta-cells exposed to lipotoxic conditions. Results: Sleeve gastrectomy reduced pancreas steatosis and inflammation and improved insulin sensitivity and synthesis. An upregulation of GUCA2A and GUCY2C, but not GUCA2B, was observed in pancreata from rats with dietinduced obesity one month after sleeve gastrectomy. Interestingly, both guanylin and uroguanylin diminished the lipotoxicity in palmitate-treated RIN-m5F beta-cells, evidenced by lower steatosis and downregulated lipogenic factors Srebf1, Mogat2 and Dgat1. Both guanylin peptides reduced insulin synthesis (Ins1 and Ins2) and release from RIN-m5F beta-cells, but only guanylin upregulated Wnt4, a factor that controls beta-cell proliferation and function. Discussion: Together, sleeve gastrectomy reduced pancreatic steatosis and improved beta-cell function. Several mechanisms, including the modulation of inflammation and lipogenesis as well as the upregulation of GUCA2A in the pancreas, might explain this beneficial effect of bariatric surgery.
Journal:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Year:
2023
Vol.:
24
N°:
4
pp.
3412
Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in adipocytes, in the improvement of brown adipose tissue (BAT) whitening, a process whereby brown adipocytes differentiate into white like unilocular cells, after cold exposure or bariatric surgery in male Wistar rats with diet-induced obesity (DIO) (n = 229). DIO promoted BAT whitening, evidenced by increased BAT hypertrophy, steatosis and upregulation of the lipogenic factors Pparg2 , Mogat2 and Dgat1. AQP7 was detected in BAT capillary endothelial cells and brown adipocytes, and its expression was upregulated by DIO. Interestingly, AQP7 gene and protein expressions were downregulated after cold exposure (4( ?)C) for 1 week or one month after sleeve gastrectomy in parallel to the improvement of BAT whitening. Moreover, Aqp7 mRNA expression was positively associated with transcripts of the lipogenic factors Pparg2 , Mogat2 and Dgat1 and regulated by lipogenic (ghrelin) and lipolytic (isoproterenol and leptin) signals. Together, the upregulation of AQP7 in DIO might contribute to glycerol influx used for triacylglycerol synthesis in brown adipocytes, and hence, BAT whitening. This process is reversible by cold exposure and bariatric surgery, thereby suggesting the potential of targeting BAT AQP7 as an anti-obesity therapy.
Journal:
CANCERS
ISSN:
2072-6694
Year:
2023
Vol.:
15
N°:
4
pp.
1038
Simple Summary Netrin-1 (NTN-1) regulates obesity-associated low-grade inflammation, being also involved in the control of cell migration and proliferation. We aim to study whether excess visceral adipose tissue in patients with obesity and colon cancer is associated with increased NTN1 and the expression levels of its main receptors, promoting an inflammatory microenvironment that favours colon cancer development. Increased expression levels of NTN1 and its receptor NEO1 in the visceral adipose tissue from patients with obesity and colon cancer together with elevated DCC and UNC5B mRNA levels in patients with colon cancer were found. Moreover, the treatment of colorectal cancer cells with NTN-1 and with the adipocyte-derived secretome obtained from patients with obesity increased the migration of colorectal cancer cells. These results suggest that NTN-1 plays an important role in obesity-associated colon cancer development. Netrin (NTN)-1, an extracellular matrix protein with a crucial role in inflammation, is dysregulated during obesity (OB) and influences colon cancer (CC) progression. To decipher the mechanisms underlying CC development during obesity, we examined the expression of NTN1 and its receptors in the visceral adipose tissue (VAT) of 74 (25 normal weight (NW)) (16 with CC) and 49 patients with OB (12 with CC). We also evaluated the effect of caloric restriction (CR) on the gene expression levels of Ntn1 and its receptors in the colon from a rat model fed a normal diet. The impact of adipocyte-conditioned media (ACM) from patients with OB and NTN-1 was assessed on the expression levels of neogenin 1(NEO1), deleted in colorectal carcinomas (DCC) and uncoordinated-5 homolog B (UNC5B) in Caco-2 and HT-29 human colorectal cell lines, as well as on Caco-2 cell migration. Increased NTN1 and NEO1 mRNA levels in VAT were due to OB (p < 0.05) and CC (p < 0.001). In addition, an upregulation in the expression levels of DCC and UNC5B in patients with CC (p < 0.01 and p < 0.05, respectively) was observed. Decreased (p < 0.01) Ntn1 levels in the colon from rats submitted to CR were found. In vitro experiments showed that ACM increased DCC (p < 0.05) and NEO1 (p < 0.01) mRNA levels in HT-29 and Caco-2 cell lines, respectively, while UNC5B decreased (p < 0.01) in HT-29. The treatment with NTN-1 increased (p < 0.05) NEO1 mRNA levels in HT-29 cells and DCC (p < 0.05) in both cell lines. Finally, we revealed a potent migratory effect of ACM and NTN-1 on Caco-2 cells. Collectively, these findings point to increased NTN-1 during OB and CC fuelling cancer progression and exerting a strong migratory effect on colon cancer cells.
Journal:
CIRUGÍA ESPAÑOLA
ISSN:
2173-5077
Year:
2023
Vol.:
101
N°:
5
pp.
333 - 340
INTRODUCTION: Laparoscopic resection of the pancreas (LRP) has been implemented to a varying degree because it is technically demanding and requires a long learning curve. In the present study we analyze the risk factors for complications and hospital readmissions in a single center study of 105 consecutive LRPs.
METHODS: We conducted a retrospective study using a prospective database. Data were collected on age, gender, BMI, ASA score, type of surgery, histologic type, operative time, hospital stay, postoperative complications, degree of severity and hospital readmission.
RESULTS: The cohort included 105 patients, 63 females and 42 males with a median age and BMI of 58 (53-70) and 25.5 (22,2-27.9) respectively. Eighteen (17%) central pancreatectomies, 5 (4.8%) enucleations, 81 (77.6%) distal pancreatectomies and one total pancreatectomy were performed. Fifty-six patients (53.3%) experienced some type of complication, of which 13 (12.3%) were severe (Clavien-Dindo > IIIb) and 11 (10.5%) patients were readmitted in the first 30 days after surgery. In the univariate analysis, age, male gender, ASA score, central pancreatectomy and operative time were significantly associated with the development of complications (P <0.05). In the multivariate analysis, male gender (OR 7.97; 95% CI 1.08-58.88)), severe complications (OR 59.40; 95% CI, 7.69-458.99), and the development of intrabdominal collections (OR 8.97; 95% CI, 1.28-63.02)) were associated with hospital readmission.
CONCLUSIONS: Age, male gender, ASA score, operative time and central pancreatectomy are associated with a higher incidence of complications. Male gender, severe complications and intraabdominal collections are associated with more hospital readmissions.
Journal:
METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN:
0026-0495
Year:
2023
Vol.:
147
pp.
155663
Background: The biological mediators supporting the resolution of liver steatosis, inflammation and fibrosis after bariatric surgery in patients with obesity and NAFLD remain unclear. We sought to analyze whether uroguanylin and guanylin, two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of obesity-associated NAFLD after bariatric surgery. Methods: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 214 participants undergoing bariatric surgery with biopsy-proven NAFLD diagnosis. Pathways involved in lipid metabolism, mitochondrial network and fibrogenesis were evaluated in liver biopsies (n = 137). The effect of guanylin and uroguanylin on these metabolic functions was assessed in HepG2 hepatocytes and LX-2 hepatic stellate cells (HSC) under lipotoxic and profibrogenic conditions.Results: Plasma and hepatic expression of GUCA2B were decreased in obesity-associated NAFLD. Both GUCA2A and GUCA2B levels were increased after sleeve gastrectomy and Roux-en-Y gastric bypass in parallel to the improved liver function. The liver of patients with type 2 diabetes showed impaired mitochondrial & beta;-oxidation, biogenesis, dynamics as well as increased fibrosis. Uroguanylin diminished the lipotoxicity in palmitate-treated HepG2 hepatocytes, evidenced by decresased steatosis and lipogenic factors, as well as increased mitochondrial network expression, AMPK-induced & beta;-oxidation and oxygen consumption rate. Additionally, uroguanylin, but not guanylin, reversed HSC myofibroblast transdifferentiation as well as fibrogenesis after TGF-& beta;1 stimulation.Conclusions: Uroguanylin constitutes a protective factor against lipotoxicity, mitochondrial dysfunction and fibrosis. Increased GUCA2B levels might contribute to improve liver injury in patients with obesity-associated NAFLD after bariatric surgery.
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2022
Vol.:
114
N°:
2
pp.
73 - 75
Acute pancreatitis (AP) is the third most frequent cause of hospital admissions for digestive disorders in the US and Europe after digestive bleeding and cholelithiasis/cholecystitis. The incidence of AP ranges from 15 to 100 cases per 100,000 inhabitants per year, and has been steadily increasing in recent years. In Spain, the reported incidence is 72 patients per 100,000 inhabitants per year. The most frequent cause is biliary lithiasis (50 %-60 % of cases); fortunately, 80 % of patients have only mild symptoms¿as defined by the revised Atlanta Classification¿and progress favorably, although mortality rate is 4.2 %. Clinical guidelines explicitly indicate that laparoscopic cholecystectomy should be performed during the first 48-72 hours or at the time of hospital admission in mild cases of biliary origin.
Journal:
ACTA BIOMATERIALIA
ISSN:
1742-7061
Year:
2022
Vol.:
141
pp.
264 - 279
Biomechanical properties of adipose tissue (AT) are closely involved in the development of obesity associated comorbidities. Bariatric surgery (BS) constitutes the most effective option for a sustained weight loss in addition to improving obesity-associated metabolic diseases including type 2 diabetes (T2D). We aimed to determine the impact of weight loss achieved by BS and caloric restriction (CR) on the biomechanical properties of AT. BS but not CR changed the biomechanical properties of epididymal white AT (EWAT) from a diet-induced obesity rat model, which were associated with metabolic improvements. We found decreased gene expression levels of collagens and Lox together with increased elastin and Mmps mRNA levels in EWAT after BS, which were also associated with the biomechanical properties. Moreover, an increased blood vessel density was observed in EWAT after surgery, confirmed by an up regulation of Acta2 and Antxr1 gene expression levels, which was also correlated with the biomechanical properties. Visceral AT from patients with obesity showed increased stiffness after tensile tests compared to the EWAT from the animal model. This study uncovers new insights into EWAT adaptation after BS with decreased collagen crosslink and synthesis as well as an increased degradation together with enhanced blood vessel density providing, simultaneously, higher stiffness and more ductility.
Statement of Significance
Biomechanical properties of the adipose tissue (AT) are closely involved in the development of obesity associated comorbidities. In this study, we show for the first time that biomechanical properties of AT determined by E , UTS and strain at UTS are decreased in obesity, being increased after bariatric surgery by the promotion of ECM remodelling and neovascularization. Moreover, these changes in biomechanical properties are associated with improvements in metabolic homeostasis. Consistently, a better characterization of the plasticity and biomechanical properties of the AT after bariatric surgery opens up a new field for the development of innovative strategies for the reduction of fibrosis and inflammation in AT as well as to better understand obesity and its associated comorbidities.
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2022
Vol.:
114
N°:
6
pp.
317 - 322
Background and aim: fifty to 70 percent of pancreatic neuro-endocrine tumors are diagnosed incidentally. The objective of this study was to compare the phenotype and oncologi-cal outcomes of incidental versus symptomatic pancreatic neuroendocrine tumors. Methods: a retrospective study was performed, identifying all incidental and symptomatic tumors resected between 2000 and 2019. Baseline characteristics, symptoms, oper-ative variables and pathological stage were all recorded. Patterns of recurrence and overall and disease-free survival were analyzed in both groups. Results: fifty-one incidental and 45 symptomatic pancreat-ic tumor resections were performed. Symptomatic tumors were more frequent in females (29 vs 17; p = 0.005) and younger patients (median years; 50 vs 58; p = 0.012) and were detected at a more advanced stage (p = 0.027). There were no differences in location and most resections (n = 49; 51 %) were performed laparoscopically. There were no operative mortalities and 17 (17.7 %) severe com-plications (>_ IIIb on the Clavien-Dindo classification) were recorded with no differences between the two groups. With a median follow-up of 64.4 months (range 13.5-90), overall survival at five and ten years was 89.7 % and 72.8 % for the non-incidental tumors and 80.9 % and 54.6 % for the incidental tumors (p = ns), respectively. Disease-free survival in both groups (excluding M1a) was 71.2 % and 47.5 %, and 93.7 % and 78.1 %, respectively (p = ns). Conclusions: symptomatic tumors are more frequent in females and present at more advanced pathological stag-es. There were no significant differences in overall and disease-free survival between the two groups. Resection of incidental tumors >_ 1.5-2 cm seems advisable, although each case should be assessed on an individual basis.
Journal:
CIRUGIA ESPAÑOLA
ISSN:
0009-739X
Year:
2022
Vol.:
100
N°:
11
pp.
736 - 738
Journal:
SURGICAL LAPAROSCOPY ENDOSCOPY AND PERCUTANEOUS TECHNIQUES
ISSN:
1530-4515
Year:
2022
Vol.:
32
N°:
1
pp.
28 - 34
Background: Laparoscopic resection is the treatment of choice for colorectal cancer. Rates of conversion to open surgery range between 7% and 30% and controversy exists as to the effect of this on oncologic outcomes. The objective of this study was to analyze what factors are predictive of conversion and what effect they have on oncologic outcomes. Methods: From a prospective database of patients undergoing laparoscopic surgery between 2000 and 2018 a univariate and multivariate analyses were made of demographic, pathologic, and surgical variables together with complementary treatments comparing purely laparoscopic resection with conversions to open surgery. Overall and disease-free survival were compared using the Kaplan-Meier method. Results: Of a total of 829 patients, 43 (5.18%) converted to open surgery. In the univariate analysis, 12 variables were significantly associated with conversion, of which left-sided resection [odds ratio (OR): 2.908; P=0.02], resection of the rectum (OR: 4.749, P=0.014), and local invasion of the tumor (OR: 6.905, P<0.01) were independently predictive factors in the multiple logistic regression. Female sex was associated with fewer conversions (OR: 0.375, P=0.012). The incidence and pattern of relapses were similar in both groups and there were no significant differences between overall and disease-free survival. Conclusions: Left-sided resections, resections of the rectum and tumor invasion of neighboring structures are associated with higher rates of conversion. Female sex is associated with fewer conversions. Conversion to open surgery does not compromise oncologic outcomes at 5 and 10 years.
Journal:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Year:
2022
Vol.:
23
N°:
16
pp.
9222
Dysfunctional adipose tissue (AT) in the context of obesity leads to chronic inflammation together with an altered extracellular matrix (ECM) remodelling, favouring cancer development and progression. Recently, the influence of dermatopontin (DPT) in AT remodelling and inflammation has been proposed. We aimed to evaluate the role of DPT in the development of obesity-associated colon cancer (CC). Samples obtained from 73 subjects [26 lean (LN) and 47 with obesity (OB)] were used in a case-control study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (42 without CC and 31 with CC). In vitro studies in the adenocarcinoma HT-29 cell line were performed to analyse the impact of pro- and anti-inflammatory mediators on the transcript levels of DPT as well as the effect of DPT on ECM remodelling and inflammation. Although obesity increased (p < 0.05) the circulating levels of DPT, its concentrations were significantly decreased (p < 0.05) in patients with CC. Gene expression levels of DPT in the colon from patients with CC were downregulated and, oppositely, a tendency towards increased mRNA levels in visceral AT was found. We further showed that DPT expression levels in HT-29 cells were enhanced (p < 0.05) by inflammatory factors (LPS, TNF-alpha and TGF-beta), whereas the anti-inflammatory IL-4 decreased (p < 0.05) its expression levels. We also demonstrated that DPT upregulated (p < 0.05) the mRNA of key molecules involved in ECM remodelling (COL1A1, COL5A3, TNC and VEGFA) whereas decorin (DCN) expression was downregulated (p < 0.05) in HT-29 cells. Finally, we revealed that the adipocyte-conditioned medium obtained from volunteers with OB enhanced (p < 0.01) the expression of DPT in HT-29 and Caco-2 cells. The decreased circulating and expression levels of DPT in the colon together with the tendency towards increased levels in visceral AT in patients with CC and its influence on the expression of ECM proteins suggest a possible role of DPT in the OB-associated CC.
Journal:
METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN:
0026-0495
Year:
2022
Vol.:
128
pp.
155119
Background: The biological mediators supporting long-term weight loss and changes in dietary choice behaviour after sleeve gastrectomy remain unclear. Guanylin and uroguanylin are gut hormones involved in the regulation of satiety, food preference and adiposity. Thus, we sought to analyze whether the guanylin system is involved in changes in food preference after sleeve gastrectomy in obesity.
Methods: Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were determined in patients with severe obesity (n = 41) as well as in rats with diet-induced obesity (n = 48), monogenic obesity (Zucker fa/fa) (n = 18) or in a food choice paradigm (normal diet vs high-fat diet) (n = 16) submitted to sleeve gastrectomy. Lingual distribution and expression of guanylins (GUCA2A and GUCA2B) and their receptor GUCY2C as well as the fatty acid receptor CD36 were evaluated in the preclinical models.
Results: Circulating concentrations of GUCA2A and GUCA2B were increased after sleeve gastrectomy in patients with severe obesity as well as in rats with diet-induced and monogenic (fa/fa) obesity. Interestingly, the lower dietary fat preference observed in obese rats under the food choice paradigm as well as in patients with obesity after sleeve gastrectomy were negatively associated with post-surgical GUCA2B levels. Moreover, sleeve gastrectomy upregulated the low expression of GUCA2A and GUCA2B in taste bud cells of tongues from rats with diet induced and monogenic (fa/fa) obesity in parallel to a downregulation of the lingual lipid sensor CD36.
Conclusions: The increased circulating and lingual GUCA2B after sleeve gastrectomy suggest an association between the uroguanylin-GUCY2C endocrine axis and food preference through the regulation of gustatory responses. (c) 2022 Elsevier Inc. All rights reserved.
Authors:
Ripolles-Melchor, J.; Sánchez-Santos, R.; Abad-Motos, A. (Autor de correspondencia); et al.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2022
Vol.:
32
N°:
4
pp.
1289 - 1299
Purpose: The effectiveness of enhanced recovery after surgery (ERAS) pathways in patients undergoing bariatric surgery remains unclear. Our objective was to determine the effect of the ERAS elements on patient outcomes following elective bariatric surgery.
Materials and methods: Prospective cohort study in adult patients undergoing elective bariatric surgery. Each participating center selected a single 3-month data collection period between October 2019 and September 2020. We assessed the 24 individual components of the ERAS pathways in all patients. We used a multivariable and multilevel logistic regression model to adjust for baseline risk factors, ERAS elements, and center differences RESULTS: We included 1419 patients. One hundred and fourteen patients (8%) developed postoperative complications. There were no differences in the incidence of overall postoperative complications between the self-designated ERAS and non-ERAS groups (54 (8.7%) vs. 60 (7.6%); OR, 1.14; 95% CI, 0.73-1.79; P = .56), neither for moderate-to-severe complications, readmissions, re-interventions, mortality, or hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 0.85; 95% CI, 0.62-1.17; P = .33) Adherence to the ERAS elements in the highest adherence quartile (Q1) was greater than 72.2%, while in the lowest adherence quartile (Q4) it was less than 55%. Patients with the highest adherence rates had shorter hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 1.54; 95% CI, 1.09-2.17; P = .015), while there were no differences in the other outcomes CONCLUSIONS: Higher adherence to ERAS Society® recommendations was associated with a shorter hospital stay without an increase in postoperative complications or readmissions.
Journal:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Year:
2022
Vol.:
23
N°:
19
pp.
11641
Bariatric surgery has been recognized as the safest and most effective procedure for controlling type 2 diabetes (T2D) and obesity in carefully selected patients. The aim of the present study was to compare the effects of Sleeve Gastrectomy (SG) and Single Anastomosis Duodenoileal Bypass with SG (SADI-S) on the metabolic profile of diet-induced obese rats. A total of 35 four-week-old male Wistar rats were submitted to surgical interventions (sham operation, SG and SADI-S) after 4 months of being fed a high-fat diet. Body weight, metabolic profile and the expression of molecules involved in the control of subcutaneous white (SCWAT), brown (BAT) and beige (BeAT) adipose tissue function were analyzed. SADI-S surgery was associated with significantly decreased amounts of total fat pads (p < 0.001) as well as better control of lipid and glucose metabolism compared to the SG counterparts. An improved expression of molecules involved in fat browning in SCWAT and in the control of BAT and BeAT differentiation and function was observed following SADI-S. Together, our findings provide evidence that the enhanced metabolic improvement and their continued durability after SADI-S compared to SG rely, at least in part, on the improvement of the BeAT phenotype and function.
Journal:
FRONTIERS IN IMMUNOLOGY
ISSN:
1664-3224
Year:
2022
Vol.:
13
pp.
832185
Interleukin (IL)-36 is a recently described cytokine with well-known functions in the regulation of multiple inflammatory diseases. Since no data exists on how this cytokine regulates adipose tissue (AT) homeostasis, we aimed to explore the function of a specific isoform, IL-36 gamma, an agonist, in human obesity and obesity-associated type 2 diabetes as well as in AT inflammation and fibrosis. Plasma IL-36 gamma was measured in 91 participants in a case-control study and the effect of weight loss was evaluated in 31 patients with severe obesity undergoing bariatric surgery. Gene expression levels of IL36G and its receptor were analyzed in relevant human metabolic tissues. The effect of inflammatory factors and IL-36 gamma was determined in vitro in human adipocytes and macrophages. We found, for the first time, that the increased (P<0.05) circulating levels of IL-36 gamma in patients with obesity decreased (P<0.001) after weight and fat loss achieved by Roux-en-Y gastric bypass and that gene expression levels of IL36G were upregulated in the visceral AT (P<0.05) and in the peripheral blood mononuclear cells (P<0.01) from patients with obesity. We also demonstrated increased (P<0.05) expression levels of Il36g in the epididymal AT from diet-induced obese mice. IL36G was significantly enhanced (P<0.001) by LPS in human adipocytes and monocyte-derived macrophages, while no changes were found after the incubation with anti-inflammatory cytokines. The addition of IL-36 gamma for 24 h strongly induced (P<0.01) its own expression as well as key inflammatory and chemoattractant factors with no changes in genes associated with fibrosis. Furthermore, adipocyte-conditioned media obtained from patients with obesity increased (P<0.01) the release of IL-36 gamma and the expression (P<0.05) of cathepsin G (CTSG) in monocyte-derived macrophages. These findings provide, for the first time, evidence about the properties of IL-36 gamma in the regulation of AT-chronic inflammation, emerging as a link between AT biology and the obesity-associated comorbidities.
Journal:
ANZ JOURNAL OF SURGERY
ISSN:
1445-1433
Year:
2022
Vol.:
92
N°:
3
pp.
620 - 620
Journal:
NUTRIENTS
ISSN:
2072-6643
Year:
2022
Vol.:
14
N°:
20
pp.
4372
Netrin (NTN)-1 exhibits pro- and anti-inflammatory roles in different settings, playing important roles in the obesity-associated low-grade chronic inflammation. We aimed to determine the impact of NTN-1 on obesity and obesity-associated type 2 diabetes, as well as its role in visceral adipose tissue (VAT) inflammation. A total of 91 subjects were enrolled in this case-control study. Circulating levels of NTN-1 and its receptor neogenin (NEO)-1 were determined before and after weight loss achieved by caloric restriction and bariatric surgery. mRNA levels of NTN1 and NEO1 were assessed in human VAT, liver, and peripheral blood mononuclear cells. In vitro studies in human visceral adipocytes and human monocytic leukemia cells (THP-1)-derived macrophages were performed to analyze the impact of inflammation-related mediators on the gene expression levels of NTN1 and its receptor NEO1 as well as the effect of NTN-1 on inflammation. Increased (p < 0.001) circulating concentrations of NTN-1 in obesity decreased (p < 0.05) after diet-induced weight loss being also associated with a reduction in glucose (p < 0.01) and insulin levels (p < 0.05). Gene expression levels of NTN1 and NEO1 were upregulated (p < 0.05) in the VAT from patients with obesity with the highest expression in the stromovascular fraction cells compared with mature adipocytes (p < 0.01). NTN1 expression levels were enhanced (p < 0.01) under hypoxia and by inflammatory factors in both adipocytes and macrophages. Adipocyte-conditioned media strongly upregulated (p < 0.001) the mRNA levels of NTN1 in macrophages. The treatment of adipocytes with NTN-1 promoted the upregulation (p < 0.05) of pro-inflammatory and chemotactic molecules as well as its receptor NEO1. Collectively, these findings suggest that NTN-1 regulates VAT chronic inflammation and insulin resistance in obesity.
Journal:
JOURNAL OF INFLAMMATION RESEARCH
ISSN:
1178-7031
Year:
2022
Vol.:
15
pp.
1331 - 1345
Background: Excess adiposity leads to a dysfunctional adipose tissue that contributes to the development of obesity-associated comorbidities such as type 2 diabetes (T2D). Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring antagonist of the IL-1 receptor with anti-inflammatory properties. The aim of the present study was to compare the circulating concentrations of IL-1RA and its mRNA expression in visceral adipose tissue (VAT) in subjects with normal weight (NW), obesity with normoglycemia (OB-NG), or obesity with impaired glucose tolerance or T2D (OB-IGT&T2D) and to analyze the effect of changes in body fat percentage (BF%) on IL-1RA levels. Methods: Serum concentrations of IL-1RA were measured in 156 volunteers. Expression of IL1RN mRNA in VAT obtained from 36 individuals was determined. In addition, the concentrations of IL-1RA were measured before and after weight gain as well as weight loss following a dietetic program or Roux-en-Y gastric bypass (RYGB). Results: Serum levels of IL-1RA were significantly increased in individuals with obesity, being further increased in the OBIGT&T2D group (NW 440 +/- 316, OB-NG 899 +/- 562, OB-IGT&T2D 1265 +/- 739 pg/mL; P<0.001) and associated with markers of inflammation and fatty liver. IL1RN mRNA expression in VAT was significantly increased in the OB-IGT&T2D group and correlated in the global cohort with the mRNA expression of SPP1, CCL2, CD68, and MMP9. Levels of IL-1RA were not modified after modest changes in BF%, but RYGB-induced weight loss significantly decreased IL-1RA concentrations from 1233 +/- 1009 to 660 +/- 538 pg/ mL (P<0.001). Conclusion: Serum IL-1RA concentrations are increased in patients with obesity being further elevated in obesity-associated IGT and T2D in association with markers of adipose tissue dysfunction. The mRNA expression of IL1RN is markedly increased in VAT of subjects with obesity and T2D in relation with genes involved in macrophage recruitment, inflammation and matrix remodeling. Serum IL-1RA concentrations are reduced when a notable amount of BF% is loss. Measurement of IL-1RA is an excellent biomarker of adipose tissue dysfunction in obesity-associated metabolic alterations.
Journal:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Year:
2021
Vol.:
22
N°:
16
pp.
8485
Objective: The protein microfibril-associated glycoprotein (MAGP)-1 constitutes a crucial extracellular matrix protein. We aimed to determine its impact on visceral adipose tissue (VAT) remodelling during obesity-associated colon cancer (CC). Methods: Samples obtained from 79 subjects (29 normoponderal (NP) (17 with CC) and 50 patients with obesity (OB) (19 with CC)) were used in the study. Circulating concentrations of MAGP-1 and its gene expression levels (MFAP2) in VAT were analysed. The impact of inflammation-related factors and adipocyte-conditioned media (ACM) on MFAP2 mRNA levels in colon adenocarcinoma HT-29 cells were further analysed. The effects of MAGP-1 in the expression of genes involved in the extracellular matrix (ECM) remodelling and tumorigenesis in HT-29 cells was also explored. Results: Obesity (p < 0.01) and CC (p < 0.001) significantly decreased MFAP2 gene expression levels in VAT whereas an opposite trend in TGFB1 mRNA levels was observed. Increased mRNA levels of MFAP2 after the stimulation of HT-29 cells with lipopolysaccharide (LPS) (p < 0.01) and interleukin (IL)-4 (p < 0.01) together with a downregulation (p < 0.05) after hypoxia mimicked by CoCl2 treatment was observed. MAGP-1 treatment significantly enhanced the mRNA levels of the ECM-remodelling genes collagen type 6 alpha 3 chain (COL6A3) (p < 0.05), decorin (DCN) (p < 0.01), osteopontin (SPP1) (p < 0.05) and TGFB1 (p < 0.05). Furthermore, MAGP-1 significantly reduced (p < 0.05) the gene expression levels of prostaglandin-endoperoxide synthase 2 (COX2/PTGS2), a key gene controlling cell proliferation, growth and adhesion in CC. Interestingly, a significant decrease (p < 0.01) in the mRNA levels of MFAP2 in HT-29 cells preincubated with ACM from volunteers with obesity compared with control media was observed. Conclusion: The decreased levels of MAGP-1 in patients with obesity and CC together with its capacity to modulate key genes involved in ECM remodelling and tumorigenesis suggest MAGP-1 as a link between AT excess and obesity-associated CC development.
Journal:
CELLULAR AND MOLECULAR IMMUNOLOGY
ISSN:
1672-7681
Year:
2021
Vol.:
18
N°:
10
pp.
2457 - 2459
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2021
Vol.:
113
N°:
7
pp.
554 - 554
Journal:
JAMA SURGERY
ISSN:
2168-6254
Year:
2021
Vol.:
156
N°:
12
pp.
1183 - 1183
Journal:
CELLULAR AND MOLECULAR IMMUNOLOGY
ISSN:
1672-7681
Year:
2021
Vol.:
18
N°:
4
pp.
1045 - 1057
The NLRP3-IL-1 beta pathway plays an important role in adipose tissue (AT)-induced inflammation and the development of obesity-associated comorbidities. We aimed to determine the impact of NLRP3 on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and extracellular matrix (ECM) remodeling. Samples obtained from 98 subjects were used in a case-control study. The expression of different components of the inflammasome as well as their main effectors and inflammation- and ECM remodeling-related genes were analyzed. The impact of blocking NLRP3 using siRNA in lipopolysaccharide (LPS)-mediated inflammation and ECM remodeling signaling pathways was evaluated. We demonstrated that obesity (P < 0.01), obesity-associated T2D (P < 0.01) and NAFLD (P < 0.05) increased the expression of different components of the inflammasome as well as the expression and release of IL-1 beta and IL-18 in AT. We also found that obese patients with T2D exhibited increased (P < 0.05) hepatic gene expression levels of NLRP3, IL1B and IL18. We showed that NLRP3, but not NLRP1, is regulated by inflammation and hypoxia in visceral adipocytes. We revealed that the inhibition of NLRP3 in human visceral adipocytes significantly blocked (P < 0.01) LPS-induced inflammation by downregulating the mRNA levels of CCL2, IL1B, IL6, IL8, S100A8, S100A9, TLR4 and TNF as well as inhibiting (P < 0.01) the secretion of IL1-beta into the culture medium. Furthermore, blocking NLRP3 attenuated (P < 0.01) the LPS-induced expression of important molecules involved in AT fibrosis (COL1A1, COL4A3, COL6A3 and MMP2). These novel findings provide evidence that blocking the expression of NLRP3 reduces AT inflammation with significant fibrosis attenuation.
Journal:
JOURNAL OF HEPATOLOGY (ONLINE)
ISSN:
0168-8278
Year:
2021
Vol.:
74
N°:
2
pp.
469 - 471
Journal:
SURGICAL LAPAROSCOPY ENDOSCOPY AND PERCUTANEOUS TECHNIQUES
ISSN:
1530-4515
Year:
2021
Vol.:
31
N°:
5
pp.
558 - 564
Background: Laparoscopic resection is the ideal treatment of colon cancer. The aim of the study was to analyze the predictive factors for postoperative complications and their impact on oncologic outcomes in laparoscopic resections in colon cancer.
Materials and Methods: In all patients undergoing elective laparoscopic surgery the number and degree of severity of postoperative complications were recorded and classified according to Clavien-Dindo. A univariate analysis was made of the demographic, surgical, and oncologic variables of patients with and without complications. The statistically significant variables were then entered into a multivariate model. In both groups overall and disease-free survival were analyzed using Kaplan-Meier estimates.
Results: Of 524 patients, 138 (26.3%) experienced some type of complication, 110 less severe (79.7%) and 28 (20.4%) severe. Twenty-nine conversions to open surgery occurred (5.5%) and hospital mortality was 0.2%. In the multivariate analysis, use of corticosteroids [odds ratio (OR): 3.619], oral anticoagulants (OR: 3.49), blood transfusions (OR: 4.30), and conversion to open surgery (OR: 3.93) were significantly associated with the development of complications. However, sigmoid resections were associated with fewer complications (OR: 0.45). Overall 5-year and 10-year survival in both groups, was 83.3%, 74.1%, 76.0%, and 67.1%, respectively (P = 0.18). Disease-free survival at 5 and 10 years, excluding stage IV tumors, was 88.6% and 90.4%, respectively (P = 0.881).
Conclusions: The use of corticosteroids, oral anticoagulants, blood transfusions, and conversion to open surgery are all independent predictive factors of postoperative complications. Sigmoid resections are associated with fewer complications. In laparoscopic resections of the colon, complications do not negatively affect long-term oncologic outcomes.
Journal:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Year:
2021
Vol.:
22
N°:
23
Angiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental models and patients with severe obesity. Plasma ANGPTL8 was measured in 170 individuals before and 6 months after bariatric surgery. Hepatic ANGPTL8 expression was evaluated in liver biopsies of patients with severe obesity undergoing bariatric surgery with available liver pathology analysis (n = 75), as well as in male Wistar rats with diet-induced obesity subjected to sham operation, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) (n = 65). The effect of ANGPTL8 on lipogenesis was assessed in human HepG2 hepatocytes under palmitate-induced lipotoxic conditions. Plasma concentrations and hepatic expression of ANGPTL8 were increased in patients with obesity-associated NAFLD in relation to the degree of hepatic steatosis. Sleeve gastrectomy and RYGB improved hepatosteatosis and reduced the hepatic ANGPTL8 expression in the preclinical model of NAFLD. Interestingly, ANGPTL8 inhibited steatosis and expression of lipogenic factors (PPARG2, SREBF1, MOGAT2 and DGAT1) in palmitate-treated human hepatocytes. Together, ANGPTL8 is involved in the resolution of NAFLD after bariatric surgery partially by the inhibition of lipogenesis in steatotic hepatocytes.
Journal:
JOURNAL OF INFLAMMATION RESEARCH
ISSN:
1178-7031
Year:
2021
Vol.:
14
pp.
6431 - 6446
Background: Inflammasomes maintain tissue homeostasis and their altered regulation in the colon, and the adipose tissue (AT) leads to chronic activation of inflammatory pathways promoting colon cancer (CC) development. We aimed to analyze the potential involvement of inflammasomes in obesity-associated CC. Methods: Ninety-nine volunteers [61 with obesity (OB) and 38 normoponderal (NP)] further subclassified according to the approved protocol for the diagnosis of CC (58 without CC and 41 with CC) were included in the case-control study. Results: CC (P<0.01) and obesity (P<0.01) were accompanied by increased mRNA levels of NLRP3, NLRP6, ASC, IL1B and NOD2 in VAT. Contrarily, patients with CC exhibited a downregulation of NLRP6 and IL18 in their colon. Additionally, we revealed that the decreased Nlrp1 (P<0.05), Nlrp3 (P<0.01) and Nlrp6 (P<0.01) mRNA levels in the colon from obese rats significantly increase (P<0.05) after caloric restriction. Adipocyteconditioned media obtained from subjects with obesity reduced (P<0.01) the mRNA of NLRP3 as well as molecules involved in maintaining the intestinal integrity (MUC2, CLDN1 and TJP1) and the anti-inflammatory factors FGF21, KLF4, and IL33 and in HT 29 cells. We also found that the knockdown of NLRP6 in HT-29 cells significantly upregulated (P<0.05) the mRNA of NLRP1 and NLRP3 and inhibited (P<0.05) the expression levels of MUC2. Finally, we showed that the incubation of HT-29 with Akkermansia muciniphila influence (P<0.05) the inflammasome expression profile as well as intestinal integrity-related genes and aberrant inflammation. Conclusions: These findings provide evidence that the downregulated levels of NLRP6 and IL18 in the colon from patients with CC may be responsible for a reduced intestinal-barrier integrity, triggering local inflammation, which in turn acts on the dysfunctional AT in obesity, increasing the expression of different inflammasome components and flaring up a vicious cycle of uncontrollable inflammatory cascades that favours a pro-tumorigenic microenvironment.
Journal:
CELLS
ISSN:
2073-4409
Year:
2020
Vol.:
9
N°:
6
pp.
1403
Aquaporin-11 (AQP11) is expressed in human adipocytes, but its functional role remains unknown. Since AQP11 is an endoplasmic reticulum (ER)-resident protein that transports water, glycerol, and hydrogen peroxide (H2O2), we hypothesized that this superaquaporin is involved in ER stress induced by lipotoxicity and inflammation in human obesity. AQP11 expression was assessed in 67 paired visceral and subcutaneous adipose tissue samples obtained from patients with morbid obesity and normal-weight individuals. We found that obesity and obesity-associated type 2 diabetes increased (p < 0.05) AQP11 mRNA and protein in visceral adipose tissue, but not subcutaneous fat. Accordingly, AQP11 mRNA was upregulated (p < 0.05) during adipocyte differentiation and lipolysis, two biological processes altered in the obese state. Subcellular fractionation and confocal microscopy studies confirmed its presence in the ER plasma membrane of visceral adipocytes. Proinflammatory factors TNF-¿, and particularly TGF-ß1, downregulated (p < 0.05) AQP11 mRNA and protein expression and reinforced its subcellular distribution surrounding lipid droplets. Importantly, the AQP11 gene knockdown increased (p < 0.05) basal and TGF-ß1-induced expression of the ER markers ATF4 and CHOP. Together, the downregulation of AQP11 aggravates TGF-ß1-induced ER stress in visceral adipocytes. Owing to its "peroxiporin" properties, AQP11 overexpression in visceral fat might constitute a compensatory mechanism to alleviate ER stress in obesity.
Journal:
JOURNAL OF CLINICAL MEDICINE
ISSN:
2077-0383
Year:
2020
Vol.:
9
N°:
4
pp.
1069
Compelling evidence suggests that dermatopontin (DPT) regulates collagen and fibronectin fibril formation, the induction of cell adhesion and the prompting of wound healing. We aimed to evaluate the role of DPT on obesity and its associated metabolic alterations as well as its impact in visceral adipose tissue (VAT) inflammation and extracellular matrix (ECM) remodelling. Samples obtained from 54 subjects were used in a case-control study. Circulating and VAT expression levels of DPT as well as key ECM remodelling- and inflammation-related genes were analysed. The effect of pro- and anti-inflammatory mediators on the transcript levels of DPT in visceral adipocytes was explored. The impact of DPT on ECM remodelling and inflammation pathways was also evaluated in cultured adipocytes. We show that obesity and obesity-associated type 2 diabetes (T2D) increased (p < 0.05) circulating levels of DPT. In this line, DPT mRNA in VAT was increased (p < 0.05) in obese patients with and without T2D. Gene expression levels of DPT were enhanced (p < 0.05) in human visceral adipocytes after the treatment with lipopolysaccharide, tumour growth factor (TGF)-beta and palmitic acid, whereas a downregulation (p < 0.05) was detected after the stimulation with interleukin (IL)-4 and IL-13, critical cytokines mediating anti-inflammatory pathways. Additionally, we revealed that DPT increased (p < 0.05) the expression of ECM- (COL6A3, ELN, MMP9, TNMD) and inflammation-related factors (IL6, IL8, TNF) in human visceral adipocytes. These findings provide, for the first time, evidence of a novel role of DPT in obesity and its associated comorbidities by influencing AT remodelling and inflammation.
Authors:
Frühbeck, Gema; Fernandez-Quintana, B. ; Paniagua, M.; et al.
Journal:
METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN:
0026-0495
Year:
2020
Vol.:
108
pp.
154261
Background: Fibronectin type IIIdomain-containing protein 4 (FNDC4) constitutes a secreted factor showing a high homology in the fibronectin type III and transmembrane domains with the exercise-associated myokine irisin (FNDC5). We sought to evaluate whether FNDC4 mimics the anti-obesity effects of FNDC5/irisin in human adipose tissue.
Methods: Plasma and adipose tissue samples of 78 patients with morbid obesity undergoing bariatric surgery and 26 normal-weight individuals were used in the present study.
Results: Plasma FNDC4 was decreased in patients with morbid obesity, related to obesity-associated systemic inflammation and remained unchanged six months after bariatric surgery. Visceral adipose tissue from patients with morbid obesity showed higher expression of FNDC4 and its putative receptor GPR116 regardless of the degree of insulin resistance. FNDC4 content was regulated by lipogenic, lipolytic and proinflammatory stimuli in human visceral adipocytes. FNDC4 reduced intracytosolic lipid accumulation and stimulated a brown-like pattern in human adipocytes, as evidenced by an upregulated expression of UCP-1 and the brown/beige adipocyte markers PRDM16, TMEM26 and CD137. Moreover, FNDC4 treatment upregulated mitochondrial DNA content and factors involved in mitochondrial biogenesis (TFAM, NRF1 and NRF2). Human FNDC4-knockdown adipocytes exhibited an increase in lipogenesis and a reduction of brown/beige-specific fat markers as well as factors involved in mitochondrial biogenesis.
Conclusions: Taken together, the novel adipokine FNDC4 reduces lipogenesis and increases fat browning in human visceral adipocytes. The upregulation of FNDC4 in human visceral fat might constitute an attempt to attenuate the adipocyte hypertrophy, inflammation and impaired beige adipogenesis in the obese state.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2020
Vol.:
30
N°:
11
pp.
4293 - 4299
Background Weight loss after bariatric surgery varies among patients. Patients who do not complete long-term follow-up are considered to loose less weight than those with regular follow-up visits. Objective To evaluate the influence of patients' follow-up compliance on long-term excess weight loss (%EWL) and total weight loss (%TWL) after bariatric surgery, comparing results between gastric bypass (GB) and sleeve gastrectomy (SG). Methods Patients with up to 5 years of follow-up data after bariatric surgery were included in this retrospective analysis. Patients were divided in 2 groups: those in group 1 who had attended every scheduled postoperative appointment and those in group 2 who had been lost to follow-up before 1 year and were later contacted by telephone. %EWL and %TWL were compared to determine the possible relationship between type of surgery and regularity of the follow-up. Results A total of 385 patients were included. A significant difference in EWL was observed at 5 years in the SG group (78% for group 1 versus 39% for group 2;p = 0.02) and GB group (75% for group 1 versus 62% for group 2;p = 0.01). No significant differences between surgeries were found when comparing long-term EWL in group 1 patients 77% for SG versus 75% for GB. For group 2 patients, GB achieved greater EWL than SG;p = 0.005. %TWL patients in group 2 showed significant differences in all periods of study (p < 0.05). Conclusion Bariatric surgery patients who attended all scheduled follow-up appointments experienced significantly greater long-term EWL and TWL than those who did not. GB has apparent increased benefits for weight loss in long-term follow-up when compared with SG for patients who did not attend long-term follow-up. Therefore, continued long-term follow-up of bariatric patients should be encouraged to increase postoperative weight loss results.
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2020
Vol.:
112
N°:
2
pp.
85 - 89
Objective: the objective of the present study was to analyze the characteristics of resected incidental lesions of the pancreas.
Material and methods: a retrospective study was performed of pancreatectomies due to incidentalomas between 1995 and 2018.
Results: one hundred pancreatectomies were performed due to incidental lesions; 64 (64%) were solid and 36 (36%) were cystic lesions. The cytological analysis agreed with the diagnosis in 67/71 (88.7%) cases. Thirty-six tumors were cystic, 48 were neuroendocrine and 16 were adenocarcinomas. Disease-free survival for patients with cystic, neuroendocrine tumors and adenocarcinomas was 100%, 79% and 57.7% (p < 0.04).
Conclusion: pancreatic incidentalomas have a heterogeneous phenotype and should be treated in experienced centers
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2020
Vol.:
30
N°:
10
pp.
4127 - 4128
Authors:
Weber, M. ; Mera, P.; Casas, J. ; et al.
Journal:
FASEB JOURNAL
ISSN:
0892-6638
Year:
2020
Vol.:
34
N°:
9
pp.
11816 - 11837
The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased drastically due to the global obesity pandemic but at present there are no approved therapies. Here, we aimed to revert high-fat diet (HFD)-induced obesity and NAFLD in mice by enhancing liver fatty acid oxidation (FAO). Moreover, we searched for potential new lipid biomarkers for monitoring liver steatosis in humans. We used adeno-associated virus (AAV) to deliver a permanently active mutant form of human carnitine palmitoyltransferase 1A (hCPT1AM), the key enzyme in FAO, in the liver of a mouse model of HFD-induced obesity and NAFLD. Expression of hCPT1AM enhanced hepatic FAO and autophagy, reduced liver steatosis, and improved glucose homeostasis. Lipidomic analysis in mice and humans before and after therapeutic interventions, such as hepatic AAV9-hCPT1AM administration and RYGB surgery, respectively, led to the identification of specific triacylglyceride (TAG) specie (C50:1) as a potential biomarker to monitor NAFFLD disease. To sum up, here we show for the first time that liver hCPT1AM gene therapy in a mouse model of established obesity, diabetes, and NAFLD can reduce HFD-induced derangements. Moreover, our study highlights TAG (C50:1) as a potential noninvasive biomarker that might be useful to monitor NAFLD in mice and humans.
Journal:
WORLD JOURNAL OF SURGERY
ISSN:
0364-2313
Year:
2020
Vol.:
44
N°:
6
pp.
1798 - 1806
BACKGROUND:
Latero-lateral duodenojejunostomy is the treatment of choice for superior mesenteric artery syndrome (SMAS). The present study analyzes the long-term outcomes in 13 patients undergoing laparoscopic surgery for SMAS.
MATERIALS AND METHODS:
A retrospective study of 10 females and three males undergoing surgery between 2001 and 2013 was performed. Demographic, clinical and radiologic data and long-term surgical outcomes were recorded. In 12 patients latero-lateral duodenojejunostomy and in one patient distal laparoscopic gastrectomy with Roux-en-Y reconstruction were performed. The median age was 24 years (20-28), and the median duration of symptoms was 24 months (5-24). The most frequent symptoms were abdominal pain (n¿=¿11; 92.3%), nausea and vomiting (n¿=¿10; 77%) and weight loss (n¿=¿9; 69.2%). The median operating time was 98 min (86-138) and hospital stay was 3 days (1-14).
RESULTS:
No reconversions occurred, and one patient experienced gastric emptying delay in the immediate postoperative period with spontaneous resolution. In four patients, SMAS was associated with severe stenosis of the celiac trunk which was treated in the same operation, and four patients presented stenosis of the left renal vein (the "nutcracker" phenomenon). With a median follow-up of 94 months (SD 65.3), eight patients (61.5%) had excellent results. One patient had a relapse of symptoms 4 years after surgery requiring distal gastrectomy, two patients presented delay in gastric emptying following temporary improvement and one patient experienced no improvement.
CONCLUSIONS:
Latero-lateral duodenojejunostomy yields good results in SMAS although it requires other gastric motility disorders to be ruled out for appropriate treatment to be established.
Journal:
INTERNATIONAL JOURNAL OF OBESITY
ISSN:
0307-0565
Year:
2020
Vol.:
44
N°:
2
pp.
475 - 487
BACKGROUND/OBJECTIVES:
Bariatric surgery improves nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain elusive. We evaluated the potential role of ghrelin isoforms in the amelioration of hepatic inflammation after sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB).
SUBJECTS/METHODS:
Plasma ghrelin isoforms were measured in male Wistar rats (n¿=¿129) subjected to surgical (sham operation, sleeve gastrectomy, or RYGB) or dietary interventions [fed ad libitum a normal (ND) or a high-fat diet (HFD) or pair-fed diet]. The effect of acylated and desacyl ghrelin on markers of inflammation, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in primary rat hepatocytes under palmitate-induced lipotoxic conditions was assessed.
RESULTS:
Plasma desacyl ghrelin was decreased after sleeve gastrectomy and RYGB, whereas the acylated/desacyl ghrelin ratio was augmented. Both surgeries diminished obesity-associated hepatic steatosis, CD68+- and apoptotic cells, proinflammatory JNK activation, and Crp, Tnf, and Il6 transcripts. Moreover, a postsurgical amelioration in the mitochondrial DNA content, oxidative phosphorylation (OXPHOS) complexes I and II, and ER stress markers was observed. Specifically, following bariatric surgery GRP78, spliced XBP-1, ATF4, and CHOP levels were reduced, as were phosphorylated eIF2¿. Interestingly, acylated and desacyl ghrelin inhibited steatosis and inflammation of palmitate-treated hepatocytes in parallel to an upregulation of OXPHOS complexes II, III, and V, and a downregulation of ER stress transducers IRE1¿, PERK, ATF6, their downstream effectors, ATF4 and CHOP, as well as chaperone GRP78.
CONCLUSIONS:
Our data suggest that the increased relative acylated ghrelin levels after bariatric surgery might contribute to mitigate obesity-associated hepatic inflammation, mitochondrial dysfunction, and ER stress.
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2020
Vol.:
112
N°:
10
pp.
784 - 787
COVID-19 is associated with severe coagulopathy. We present three cases of colonic ischemia that can be attributed to the hypercoagulable state related with SARS-CoV2 and disseminated intravascular coagulation. Three males aged 76, 68 and 56 with respiratory distress presented episodes of rectal bleeding, abdominal distension and signs of peritoneal irritation. Endoscopy (case 1) and computed tomography angiography revealed colonic ischemia. One patient (case 2) in which a computed tomography (CT) scan showed perforation of the gangrenous cecum underwent surgery. D-dimer levels were markedly increased (2,170, 2,100 and 7,360 ng/ml) in all three patients. All three patients died shortly after diagnosis.
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2019
Vol.:
111
N°:
2
pp.
87 - 93
Background: the aim of the present study was to analyze the clinicopathological features of patients undergoing pancreatic surgical resections due to cystic neoplasms of the pancreas. Material and methods: demographic data, form of presentation, radiologic images and location of the tumors within the pancreas were analyzed. Data was also collected on the type of surgery (open/laparoscopic), postoperative complications and their severity and oncologic outcomes. Results: eighty-two pancreatic resections were performed. The mean age of patients was 57 years and 49 (59%) were female. Forty-one tumors (50%) were incidental and the most frequent symptoms in the group of symptomatic patients were abdominal pain (63.4%) and weight loss (36.5%). Thirty-two tumors (39%) were located in the tail of the pancreas, 25 (30.5%) in the head and 20 (24.4%) in the body. Thirty-nine (47.5%) distal pancreatectomies, 16 central, ten duodenal pancreatectomies and one enucleation were performed; 40 (48.5%) were carried out laparoscopically. Mean hospital stay was ten days and eight patients (7%) experienced severe complications, one was a pancreatic fistula. Sixty-six tumors (80.5%) were recorded as non-invasive and 16 (19.5%) as invasive: seven intraductal mucinous papillary tumors, one cystic mucinous tumor, four solid pseudopapillary tumors and four cystic neuroendocrine tumors. There was a median follow-up of 64 months; disease-free survival at five and ten years was 97.4% in the patients with non-invasive tumors and 84.6% and 70.5% in the invasive tumors group (p < 0.01). Conclusions: fifty percent of cystic neoplasms of the pancreas are incidental. Two phenotypes exist, invasive and non-invasive.
Journal:
JOURNAL OF CLINICAL MEDICINE
ISSN:
2077-0383
Year:
2019
Vol.:
8
N°:
4
pp.
479
Objective: Glucagon-like peptide (GLP)-1 has been proposed as a key candidate in glucose improvements after bariatric surgery. Our aim was to explore the role of GLP-1 in surgically-induced type 2 diabetes (T2D) improvement and its capacity to regulate human adipocyte inflammation. Methods: Basal circulating concentrations of GLP-1 as well as during an oral glucose tolerance test (OGTT) were measured in lean and obese volunteers with and without T2D (n = 93). In addition, GLP-1 levels were determined before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 77). The impact of GLP-1 on inflammation signalling pathways was also evaluated. Results: We show that the reduced (p < 0.05) circulating levels of GLP-1 in obese T2D patients increased (p < 0.05) after RYGB. The area under the curve was significantly lower in obese patients with (p < 0.01) and without (p < 0.05) T2D compared to lean volunteers while obese patients with T2D exhibited decreased GLP-1 levels at baseline (p < 0.05) and 120 min (p < 0.01) after the OGTT. Importantly, higher (p < 0.05) pre-operative GLP-1 concentrations were found in patients with T2D remission after RYGB. We also revealed that exendin-4, a GLP-1 agonist, downregulated the expression of inflammation-related genes (IL1B, IL6, IL8, TNF) and, conversely, upregulated the mRNA levels of ADIPOQ in human visceral adipocytes. Furthermore, exendin-4 blocked (p < 0.05) LPS-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Conclusions: Our data indicate that GLP-1 may contribute to glycemic control and exert a role in T2D remission after RYGB. GLP-1 is also involved in limiting inflammation in human visceral adipocytes.
Journal:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Year:
2019
Vol.:
104
N°:
1
pp.
21 - 37
CONTEXT:
Human obesity is associated with increased circulating TNF-¿, a proinflammatory cytokine that induces hepatocyte cell death.
OBJECTIVE:
The potential beneficial effects of acylated and desacyl ghrelin in the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis in obesity via the inhibition of TNF-¿-induced hepatocyte apoptosis, autophagic cell death, and pyroptosis were investigated.
DESIGN, SETTINGS, AND PARTICIPANTS:
Plasma ghrelin isoforms and TNF-¿ were measured in 158 participants, and hepatocyte cell death was evaluated in liver biopsies from 76 patients with morbid obesity undergoing bariatric surgery with available liver echography and pathology analysis. The effect of acylated and desacyl ghrelin on basal and TNF-¿-induced cell death was determined in vitro in human HepG2 hepatocytes.
RESULTS:
Circulating TNF-¿ and the acylated/desacyl ghrelin ratio were increased, whereas desacyl ghrelin levels were decreased in patients with obesity and NAFLD. Six months after bariatric surgery, decreased acylated/desacyl ghrelin levels, and improved hepatic function were found. Patients with obesity and type 2 diabetes showed increased hepatic ghrelin O-acyltransferase transcripts as well as an increased hepatic apoptosis, pyroptosis, and compromised autophagy. In HepG2 hepatocytes, acylated and desacyl ghrelin treatment reduced TNF-¿-induced apoptosis, evidenced by lower caspase-8 and caspase-3 cleavage, as well as TUNEL-positive cells and pyroptosis, revealed by decreased caspase-1 activation and lower high-mobility group box 1 expression. Moreover, acylated ghrelin suppressed TNF-¿-activated hepatocyte autophagy, as evidenced by a decreased LC3B-II/I ratio and increased p62 accumulation via AMPK/mTOR.
CONCLUSIONS:
Ghrelin constitutes a protective factor against hepatocyte cell death. The increased acylated/desacyl ghrelin ratio in patients with obesity and NAFLD might constitute a compensatory mechanism to overcome TNF-¿-induced hepatocyte apoptosis, autophagy, and pyroptosis.
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2019
Vol.:
111
N°:
11
pp.
896 - 897
We have read with great interest the study by Vera MC et al. on the intrasplenic transplantation of hepatocytes from donors receiving the carcinogenic drugs diethylnitrosamine (DEN) and 2-actylaminofluorene (2-AAF). The most important conclusion of the study is that there were no signs of tumor progression in the recipient liver at seven and 60 days after hepatocellular transplantation and no differences were found in the animals with healthy hepatocyte transplants.
Journal:
NUTRIENTS
ISSN:
2072-6643
Year:
2019
Vol.:
11
N°:
9
pp.
2069
Bariatric surgery remains the most effective option for achieving important and sustained weight loss. We explored the effects of Roux-en-Y gastric bypass (RYGB) on the circulating levels of adiponectin, leptin, and the adiponectin/leptin (Adpn/Lep) ratio in patients with obesity and type 2 diabetes (T2D). Twenty-five T2D volunteers undergoing RYGB were included in the study, and further subclassified as patients that responded or not to RYBG, regarding remission of T2D. Anthropometric and biochemical variables were evaluated before and after RYGB. Obese patients with T2D exhibited an increase (p < 0.0001) in the Adpn/Lep ratio after RYGB. Changes in the Adpn/Lep ratio correlated better with changes in anthropometric data (p < 0.001) than with the variations of adiponectin or leptin alone. Multiple regression analysis revealed that the change in the Adpn/Lep ratio in patients with T2D was an independent predictor of the changes in body mass index (p < 0.001) and body fat percentage (p = 0.022). However, the Adpn/Lep ratio did not differ between individuals with or without T2D remission after RYGB. In summary, the current study demonstrated that after weight and body fat loss following RYGB, the Adpn/Lep ratio increased in patients with obesity and T2D.
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2019
Vol.:
111
N°:
5
pp.
371 - 377
Purpose: to assess the long-term benefits of bariatric surgery in super-obese (body mass index [BMI] = 50) and in elderly obese (age > 60 years) populations.
Methods: one hundred and twenty one patients who underwent laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy in a university hospital were retrospectively subdivided into the following groups: BMI < 50 vs = 50 and age < 60 vs = 60 years. Weight loss, body composition and comorbidity outcomes were registered after one and six months and one, two, three and five years with 100%, 93%, 89%, 80%, 75% and 60% successful follow-up.
Results: the percentage of excess BMI loss (% EBMIL) was comparable between BMI groups and age groups and the difference in the long-term follow up was not statistically significant (p > 0.05). Complication rates, comorbidity resolution, reduction in body fat and increase in fat-free mass were comparable between BMI groups and age groups. Gastric bypass resulted in a greater weight loss compared to sleeve gastrectomy. The % EBMIL was 65.2% vs 46.7% (p = 0.002), 65.8% vs 44.9% (p = 0.004), 64.4% vs 30.5% (p = 0.001), 55.6% vs 17.6% (p = 0.016) at one, two, three and five years postoperative, respectively. Similarly, in the super-obese group, weight loss was more pronounced after gastric bypass versus sleeve gastrectomy.
Conclusions: bariatric surgery in super-obese and elderly populations is an effective and safe weight loss measure with a good comorbidity resolution in the long-term. Gastric bypass is superior to sleeve gastrectomy in terms of long-term weight loss and comorbidity resolution in all the groups investigated.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2018
Vol.:
28
N°:
10
pp.
3299 - 3300
Journal:
CLINICAL NUTRITION
ISSN:
0261-5614
Year:
2018
Vol.:
37
N°:
2
pp.
580 - 589
Background & aims: Visceral adipose tissue (VAT) has been shown to be profoundly responsible of most of the obesity-associated metabolic derangements. The measurement of VAT usually implies the use of imaging techniques such as magnetic resonance imaging or computed tomographi(CT), Our aim was to evaluate the accuracy of the determination of VAT by means of abdominal bioimpedance (BIA) with the ViScan device in comparison with Cr and its clinical usefulness in the management of obesity. Methods: We studied a sample of 140 subjects (73 males/67 females) with BMI ranging from 17.7 to 50.4 kg/m(2) to evaluate the accuracy of the ViScan in comparison to CT to determine VAT. To further analyze ViScan's clinical usefulness we studied a separate cohort (n = 2849) analyzing cardiometabolic risk factors. Furthermore, we studied the ability of the ViScan to detect changes in VAT after weight gain (n = 107) or weight loss (n = 335). The study was performed from October 2009 through June 2015. Results: ViScan determines VAT with a good accuracy in individuals with a CT-VAT up to 200 cm(2), and then with lower precision with increasing body mass, exhibiting a moderate high correlation with Cri VAT (r = 0.75, P < 0.001). Importantly, VAT determination with the ViScan exhibits better correlations with several cardiometabolic risk factors such as glucose, triglycerides, HDL-cholesterol and markers of fatty liver than anthropometric measurements such as BMI or waist circumference. ViScan is able to detect VAT variations after body weight changes. Conclusions: Since the possibility of measuring VAT by imaging techniques is not always available, abdominal BIA represents a good alternative to estimate VAT, allowing the identification of patients with increased VAT-related cardiometabolic risk and a better management of obese patients. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Journal:
MOLECULAR NUTRITION AND FOOD RESEARCH
ISSN:
1613-4125
Year:
2018
Vol.:
62
N°:
2
Scope: To investigate intestinal markers of iron absorption in morbidly obese subjects according to glucose tolerance. Methods and results: Gene expression of both non-heme (SLC40A1 (ferroportin), SLC11A2) and heme iron (SLC46A1 (HCP1), HMOX1) transporters is analyzed in 38 small intestine tissue samples [11 with normal glucose tolerance, 14 with glucose intolerance (GI), and 13 with newly diagnosed type 2 diabetes (T2D)]. SLC40A1 (r = 0.43, p = 0.008) and SLC11A2 (r = 0.35, p = 0.03) mRNA levels are positively correlated with ferritin-to-hepcidin ratio and with fasting glucose, being significantly increased in patients with T2D. Only ferroportin is negatively associated with serum hepcidin (r = -0.617, p < 0.0001). In multivariate regression analysis, fasting glucose contributes independently to intestinal SLC40A1 (p = 0.009) and SLC11A2 (p = 0.04) variance after controlling for age, sex, and BMI. When circulating hepcidin is incorporated into the model, fasting glucose contributes significantly and independently to intestinal SLC40A1 (p = 0.02), but not to SLC11A2 (p = 0.07) variance. SLC46A1 and HMOX1 are similar in all groups. Conclusion: The expression of ferroportin and SLC11A2 is increased in the intestine of patients with T2D in association with iron stores and serum hepcidin levels. Increased intestinal iron absorption is a potential mechanism that could explain the increased body iron stores frequently observed in patients with T2D.
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2018
Vol.:
110
N°:
12
pp.
768 - 774
Objective: the objective of this study was to analyze the anatomical and clinical features and long-term oncologic outcomes of 25 patients that underwent surgery due to intraductal papillary mucinous neoplasm of the pancreas.
Material and methods: patients undergoing surgery for intraductal papillary mucinous neoplasm of the pancreas were identified from a prospective database of pancreatic resections. Demographic data, symptoms, type of surgery and type of lesion (branch type, main duct or mixed) were recorded. The lesions were classified into invasive (high grade dysplasia and carcinoma) and noninvasive (low- or intermediate-grade dysplasia). Postoperative complications were analyzed as well as the pattern of recurrence and disease-free survival at five and ten years.
Results: the most common symptoms in the 25 patients (14 males and eleven females) were abdominal pain and weight loss. Eight (32%) cases were diagnosed incidentally. Twelve (48%) of the lesions were of the branch type, three affected the main duct and ten (40%) were mixed. Twelve cephalic duodenopancreatectomies and seven total pancreatectomies were performed; three were central; two, distal; and one, enucleation. Seven cases (32%) had an invasive phenotype. Three patients had locoregional and distant recurrence at six, 16 and 46 months after surgery with a median follow-up of 7.7 years. Disease-free survival at five and ten years for the noninvasive type was 94% and 57% for invasive phenotypes (p < 0.05).
Conclusions: intraductal papillary mucinous neoplasm is a heterogeneous entity with well differentiated phenotypes, which requires a tailored strategy and treatment, as established in the current consensus guidelines due to its malignant potential.
Journal:
JOURNAL OF GASTROINTESTINAL SURGERY
ISSN:
1091-255X
Year:
2018
Vol.:
22
N°:
4
pp.
713 - 721
Laparoscopic arcuate ligament release has been demonstrated a valid therapeutic option for arcuate ligament syndrome. Nevertheless, long-term follow-up and predictive factors have not been described for this treatment. Clinical and surgical data and short- and long-term outcomes together with the impact of the degree of stenosis of the celiac trunk were analyzed in 13 consecutive patients who underwent laparoscopic arcuate ligament release between 2001 and 2013. Thirteen patients (12 F/1 M) underwent surgery. The median age was 32 years old, and their mean body mass index was 20.7 (range 14.7-25). The 13 patients presented with intense postprandial abdominal pain. Ten cases were associated with weight loss. The median duration of symptoms was 24 months (range 2-240). Three patients presented symptoms associated with superior mesenteric artery syndrome. Median operative time was 120 min (range 90-240), and there were no conversions to open surgery. Median hospital stay was 3 days (range 2-14). Over a median follow-up of 117 months (range 45-185), nine patients had excellent results although two required endovascular procedures at 70 and 24 months after surgery. Four patients (30.7%) experienced poor outcomes. When we analyzed the impact of the degree of occlusion of the celiac trunk, we observed that in patients with severe occlusion (> 70%), better results were obtained, with complete resolution of symptoms in 71% of cases. Laparoscopic arcuate ligament release constitutes an excellent treatment for arcuate ligament syndrome. The degree of occlusion of the celiac trunk may be a factor predictive of long-term outcomes.
Journal:
METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN:
0026-0495
Year:
2018
Vol.:
87
pp.
123 - 135
Objective: Kallistatin plays an important role in the inhibition of inflammation, oxidative stress, fibrosis and angiogenesis. We aimed to determine the impact of kallistatin on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and oxidative stress.
Methods: Samples obtained from 95 subjects were used in a case-control study. Circulating concentrations and expression levels of kallistatin as well as key inflammation, oxidative stress and extracellular matrix remodelling-related genes were analyzed. Circulating kallistatin concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB). The impact of kallistatin on lipopolysaccharide (LPS)- and tumour necrosis factor (TNF)-alpha-mediated inflammatory as well as oxidative stress signalling pathways was evaluated.
Results: We show that the reduced (P < 0.00001) circulating levels of kallistatin in obese patients increased (P < 0.00001) after RYGB. Moreover, gene expression levels of SERPINA4, the gene coding for kallistatin, were down regulated (P < 0.01) in the liver from obese subjects with non-alcoholic fatty liver disease. Additionally, we revealed that kallistatin reduced (P < 0.05) the expression of inflammation-related genes (CCL2, IL1B, IL6, IL8, TNFA, TGFB) and, conversely, upregulated (P < 0.05) mRNA levels of ADIPOQ and KLF4 in human adipocytes in culture. Kallistatin inhibited (P < 0.05) LPS- and INF-alpha-induced inflammation in human adipocytes via downregulating the expression and secretion of key inflammatory markers. Furthermore, kallistatin also blocked (P < 0.05) TNF-alpha-mediated lipid peroxidation as well as NOX2 and HIF1A expression while stimulating (P < 0.05) the. expression of SIRT1 and FOXO1.
Conclusions: These findings provide, for the first time, evidence of a novel role of kallistatin in obesity and its associated comorbidities by limiting adipose tissue inflammation and oxidative stress.
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2018
Vol.:
110
N°:
11
pp.
684 - 690
Purpose: the aim of this study was to compare overall and disease-free survival among patients with colorectal cancer detected via a screening program as compared to those with symptomatic cancer.
Material and methods: patients diagnosed via colonoscopy (screening group) and those with clinical symptoms (non-screening) were identified from 1995 to 2014. Demographic, clinical, surgical and pathologic variables were recorded. Stage I, II and III cancers were included. Overall and disease-free survival were calculated at five and ten years after tumor resection and survival was calculated by matching both groups for cancers at stage I, II and III.
Results: two hundred and fifty patients were identified as a result of screening procedures and 1,330 patients presented with symptomatic cancers.There were no significant differences in the baseline characteristics between the two groups. Pathologic stage, degree of differentiation, perineural invasion and lymphovascular invasion were lower in the screening group (p < 0.01). Overall and disease-free survival at five and ten years were higher in the screening group (p < 0.01). However, when the subjects were matched for pathologic stage, significant differences were found between the two groups with regard to stage I and III tumors. Disease-free survival in stage III at five years (79.1 vs 61.7%; p < 0.001) and ten years (79.1% vs 58.5%; p < 0.001) were significantly higher in the screening group.
Conclusions: patients with stage I and III tumors that were diagnosed via a screening program have a higher overall and disease-free survival at five and ten years.
Journal:
DIGESTIVE AND LIVER DISEASE
ISSN:
1590-8658
Year:
2017
Vol.:
49
N°:
7
pp.
825 - 826
Journal:
DIGESTIVE AND LIVER DISEASE
ISSN:
1590-8658
Year:
2017
Vol.:
49
N°:
7
pp.
825 - 826
Authors:
Sabench Pereferrer F.; Domínguez-Adame Lanuza E.; Ibarzabal, A.; et al.
Journal:
CIRUGIA ESPAÑOLA
ISSN:
0009-739X
Year:
2017
Vol.:
95
N°:
1
pp.
4 - 16
Bariatric surgery has proven to be highly effective in controlling obesity and metabolic syndrome; the results of this surgery are not only expressed in terms of weight loss, but also in terms of resolution of comorbidities, improved quality of life and complications. The different parameters used to measure these outcomes require uniformity and reference patterns. Therefore, it is essential to identify those indicators and quality criteria that are helpful in defining the "best practice" principles in bariatric surgery. In this regard, the Section of Obesity of the Spanish Association of Surgeons, in collaboration with the Spanish Society for Bariatric Surgery (SECO), present as an objective to identify the key points that define "quality" in this type of surgery. We describe the main indicators based on the published literature as well as the criteria for referral of the main comorbidities according to the evidence found and grades of recommendation. (C) 2016 AEC. Published by Elsevier Espana, S. L. U. All rights reserved.
Journal:
INTERNATIONAL JOURNAL OF OBESITY
ISSN:
0307-0565
Year:
2017
Vol.:
41
N°:
9
pp.
1379 - 1387
BACKGROUND/OBJECTIVES: Body weight, body mass index (BMI) and excess weight loss (EWL) are the most frequently used measures to analyse bariatric surgery outcomes. However, these measurements do not provide accurate information on body composition (BC) with body fat (BF), importantly determining the levels of cardiometabolic risk factors. Our aim was to analyse the evolution of BC after Roux-en-Y Gastric Bypass (RYGB) and its influence on the changes of cardiometabolic risk factors in comparison to BMI and EWL. SUBJECTS/METHODS: A group of 81 obese Caucasian patients (19 males/62 females) aged 44.9 +/- 1.3 years undergoing RYGB between January 2006 and December 2011 was prospectively followed up for a period of 3 years. BC was determined by air-displacement plethysmography. Visceral adiposity, physical activity and cardiometabolic risk factors were measured. RESULTS: BF was markedly (P < 0.001) reduced after the first year, increasing progressively during the second and third years after RYGB, following a different trajectory than body weight, BMI and EWL that decreased up to the second year post surgery. Markers of glucose homeostasis decreased during the first month and continued to decrease during the first year (P < 0.05), remaining stabilised or slightly increased between the second and third years following RYGB. However, markers of lipid metabolism decreased (P < 0.05) markedly during the first 12 months, increasing thereafter in parallel to the changes observed in BC, with the exception of high-density lipoprotein-cholesterol, which increased progressively throughout the whole period analysed. CONCLUSIONS: The adverse switch in the changes in BC between the first and the second years after RYGB may underlie the changes observed in cardiometabolic risk factors. Tracking of adiposity during the follow-up of bariatric/metabolic surgery yields clinically relevant information to better identify patients in need of increased lifestyle advice or treatment intensification.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2017
Vol.:
27
N°:
7
pp.
1763 - 1774
BACKGROUND:
Gastric plication is a minimally invasive bariatric surgical procedure, where the greater curvature is plicated inside the gastric lumen. Our aims were to analyze the effectiveness of gastric plication on the resolution of obesity, impaired glucose tolerance, and fatty liver in an experimental model of diet-induced obesity (DIO) and to evaluate changes in glycerol metabolism, a key substrate for adiposity and gluconeogenesis, in adipose tissue and the liver.
METHODS:
Male Wistar DIO rats (n = 58) were subjected to surgical (sham operation and gastric plication) or dietary interventions [fed a normal diet (ND) or high-fat diet (HFD) or pair-fed to the amount of food eaten by gastric-plicated animals]. The expression of aquaglyceroporins (AQPs) in epididymal (EWAT) and subcutaneous (SCWAT) fat and the liver was analyzed by real-time PCR and Western blot.
RESULTS:
Gastric plication did not result in a significant weight loss in DIO rats, showing a modest reduction in whole-body adiposity and hepatic steatosis. However, gastric-plicated animals exhibited an improvement in basal glycemia and glucose clearance, without changes in hepatic gluconeogenic genes. DIO was associated with an increase in glycerol, higher AQP3 and AQP7 in EWAT and SCWAT, and a decrease in hepatic AQP9. Gastric plication downregulated AQP3 in both fat depots without changes in adipose AQP7 and hepatic AQP9.
CONCLUSION:
Gastric plication results in a modest reduction in adiposity and hepatosteatosis but restores glycemia by downregulating AQP3, which entails lower efflux of glycerol from fat, lower plasma glycerol availability, and a reduced use of glycerol as a substrate for hepatic gluconeogenesis.
Journal:
ONCOIMMUNOLOGY
ISSN:
2162-402X
Year:
2017
Vol.:
6
N°:
7
pp.
e1328338
Growing evidence indicates that adipose tissue inflammation is an important mechanism whereby obesity promotes cancer risk and progression. Since IL-32 is an important inflammatory and remodeling factor in obesity and is also related to colon cancer (CC) development, the aim of this study was to explore whether IL-32 could function as an inflammatory factor in human obesity-associated CC promoting a microenvironment favorable for tumor growth. Samples obtained from 84 subjects [27 lean (LN) and 57 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (49 without CC and 35 with CC). We show, for the first time, that obesity (p = 0.009) and CC (p = 0.026) increase circulating concentrations of IL-32¿. Consistently, we further showed that gene (p < 0.05) and protein (p < 0.01) expression levels of IL-32¿ were upregulated in VAT from obese patients with CC. Additionally, we revealed that IL32 expression levels are enhanced by hypoxia and inflammation-related factors in HT-29 CC cells as well as that IL-32¿ is involved in the upregulation of inflammation (IL8, TNF, and CCL2) and extracellular matrix (ECM) remodeling (SPP1 and MMP9) genes in HT-29 cancer cells. Additionally, we also demonstrate that the adipocyte-conditioned medium obtained from obese patients stimulates (p < 0.05) the expression of IL32 in human CC cells. These findings provide evidence of the potential involvement of IL-32 in the development of obesity-associated CC as a pro-inflammatory and ECM remodeling cytokine.
Journal:
LANGENBECKS ARCHIVES OF SURGERY
ISSN:
1435-2443
Year:
2017
Vol.:
402
N°:
1
pp.
181 - 185
The purpose of this study is to describe a technical modification that facilitates right liver mobilization in laparoscopic right hepatectomy (LRH). In the supine position, an inflatable device is placed under the patient's right chest. For right hemiliver mobilization, the table is placed in 30A degrees anti-Trendelenburg and full-left tilt. Balloon inflation offers an additional 30A degrees left inclination that places the patient in an almost left lateral position. Foot and lateral supports are placed to prevent patient slippage during changes in the patient positioning. From December 2013 to October 2015, this technique has been used in 10 consecutive LRH. The indications for these procedures were as follows: four donor hepatectomies for living donor liver transplant, three hepatocellular carcinomas and one peripheral cholangiocarcinoma in cirrhotic patients, one hepatocellular carcinoma in a non-cirrhotic patient, and one case of colorectal cancer metastases. In this period, it has also been used to facilitate mobilization and resection in the posterior segments of the liver in seven patients. In every case, right hemiliver mobilization was easily performed in a maximum time of 15 min and placement of a tape or plastic tube for liver hanging was prepared. We have not observed any complication directly attributable to the technique herein described (i.e. right brachialgia; arms, back or left flank pain) in the early or late postoperative follow-up. The additional left inclination obtained with the inflation of a balloon under the right chest facilitates right hemiliver mobilization. Its use may help in the performance and adoption of LRH.
Journal:
INTERNATIONAL JOURNAL OF OBESITY
ISSN:
0307-0565
Year:
2017
Vol.:
41
N°:
9
pp.
1394 - 1402
BACKGROUND/OBJECTIVES: Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues as well as for pancreatic insulin secretion. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in beta-cells, and AQP12, an aquaporin related to pancreatic damage, in the improvement of pancreatic function and steatosis after sleeve gastrectomy in diet-induced obese rats. SUBJECTS/METHODS: Male Wistar obese rats (n = 125) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by sleeve-gastrectomized animals) interventions. The tissue distribution and expression of AQPs in the rat pancreas were analyzed by real-time PCR, western blotting and immunohistochemistry. The effect of ghrelin isoforms and glucagon-like peptide 1 (GLP-1) on insulin secretion, triacylglycerol (TG) accumulation and AQP expression was determined in vitro in RIN-m5F beta-cells. RESULTS: Sleeve gastrectomy reduced pancreatic beta-cell apoptosis, steatosis and insulin secretion. Lower ghrelin and higher GLP-1 concentrations were also found after bariatric surgery. Acylated and desacyl ghrelin increased TG content, whereas GLP-1 increased insulin release in RIN-m5F beta-cells. Sleeve gastrectomy was associated with an upregulation of AQP7 together with a normalization of the increased AQP12 levels in the rat pancreas. Interestingly, ghrelin and GLP-1 repressed AQP7 and AQP12 expression in RINm5F beta-cells. AQP7 protein was negatively correlated with intracellular lipid accumulation in acylated ghrelin-treated cells and with insulin release in GLP-1-stimulated beta-cells. CONCLUSIONS: AQP7 upregulation in beta-cells after sleeve gastrectomy contributes, in part, to the improvement of pancreatic steatosis and insulin secretion by increasing intracellular glycerol used for insulin release triggered by GLP-1 rather than for ghrelin-induced TG biosynthesis.
Journal:
SCIENTIFIC REPORTS
ISSN:
2045-2322
Year:
2016
Vol.:
6
pp.
39942
Bariatric surgery improves non-alcoholic fatty liver disease (NAFLD). Our aim was to investigate the potential role of ghrelin isoforms in the resolution of hepatic steatosis after sleeve gastrectomy, a restrictive bariatric surgery procedure, in diet-induced obese rats. Male Wistar rats (n = 161) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary interventions [fed ad libitum a normal (ND) or a high-fat (HFD) diet or pair-fed]. Obese rats developed hepatosteatosis and showed decreased circulating desacyl ghrelin without changes in acylated ghrelin. Sleeve gastrectomy induced a dramatic decrease of desacyl ghrelin, but increased the acylated/desacyl ghrelin ratio. Moreover, sleeve gastrectomy reduced hepatic triglyceride content and lipogenic enzymes Mogat2 and Dgat1, increased mitochondrial DNA amount and induced AMPK-activated mitochondrial FFA beta-oxidation and autophagy to a higher extent than caloric restriction. In primary rat hepatocytes, the incubation with both acylated and desacyl ghrelin (10, 100 and 1,000 pmol/L) significantly increased TG content, triggered AMPK-activated mitochondrial FFA beta-oxidation and autophagy. Our data suggest that the decrease in the most abundant isoform, desacyl ghrelin, after sleeve gastrectomy contributes to the reduction of lipogenesis, whereas the increased relative acylated ghrelin levels activate factors involved in mitochondrial FFA beta-oxidation and autophagy in obese rats, thereby ameliorating NAFLD.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2016
Vol.:
26
N°:
8
pp.
1881-9
Our study showed that serum ANGPTL8/betatrophin concentrations were increased in obese subjects after surgically induced weight loss, but not after weight loss achieved by conventional dietary treatment. The change in ANGPTL8/betatrophin concentrations emerged as a significant predictor of the change in HDL-C levels after weight loss.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2016
Vol.:
26
N°:
2
pp.
282 - 288
Background: Current evidence suggests that local anesthetic wound infiltration should be employed as part of multimodal postoperative pain management. There is scarce data concerning the benefits of this anesthetic modality in laparoscopic weight loss surgery. Therefore, we analyzed the influence of trocar site infiltration with bupivacaine on the management of postoperative pain in laparoscopic bariatric surgery.
Methods: This retrospective randomized study included 47 patients undergoing primary obesity surgery between January and September 2014. Laparoscopic gastric bypass was performed in 39 cases and sleeve gastrectomy in 8 cases. Patients were stratified into two groups depending on whether preincisional infiltration with bupivacaine and epinephrine was performed (study group, 27 patients) or not (control group, 20 patients). Visual analogue scale (VAS), International Pain Outcomes questionnaire, and rescue medication records were reviewed to assess postoperative pain.
Results: VAS scores in the study group and sleeve gastrectomy group were lower than those in the control and gastric bypass groups in the first 4 h postoperatively without reaching statistical significance (p > 0.05). VAS scores did not differ in any other period of time. No statistically significant differences in pain perception were registered according to the patient's pain outcomes questionnaire or the need for rescue medication.
Conclusions: The present study did not conclusively prove the efficacy of bupivacaine infiltration by any of the three evaluation methods analyzed. Nevertheless, preincisional infiltration provides good level of comfort in the immediate postoperative period when analgesia is most urgent.
Journal:
CLINICAL NUTRITION
ISSN:
0261-5614
Year:
2016
Vol.:
36
N°:
3
pp.
861 - 868
BACKGROUND & AIMS:
Fibroblast growth factor 19 (FGF19) and 21 (FGF21) have emerged as key regulators of energy homeostasis. Our aim was to analyze the impact of weight loss (WL) induced either by conventional dietary treatment (CDT) or bariatric surgery on FGF19 and FGF21 concentrations. Furthermore, the diverse effect of sleeve gastrectomy (SG) versus RYGB (Roux-en-Y gastric bypass) as two surgical procedures that affect the gastrointestinal anatomy and physiology differently was also analyzed.
METHODS:
Serum concentrations of FGF19 and FGF21 were measured in 137 obese patients with different degrees of insulin resistance matched by sex, age and body adiposity and compared to 33 lean individuals. Furthermore, FGF19 and FGF21 were measured in 114 subjects before and one-year after WL induced either by CDT (n = 28), SG (n = 20) or RYGB (n = 66).
RESULTS:
Circulating serum FGF19 concentrations were decreased (P < 0.01) similarly in obese patients regardless of their degree of insulin resistance, while FGF21 levels were increased in obesity (P < 0.01), being further increased in obesity-associated T2D (P < 0.01). FGF19 concentrations were increased in obese subjects after surgically-induced WL (P < 0.01), but not after WL achieved by CDT, while FGF21 levels were reduced after CDT- (P < 0.05) or SG-induced WL (P < 0.05), but not after RYGB. The change in FGF21 concentrations emerged as a significant predictor of the change in insulin resistance (HOMA) after WL.
CONCLUSIONS:
Based on the circulating concentrations and their subsequent pattern of response following WL, we conclude that FGF19 levels are mainly related to body adiposity, in particular visceral adiposity, while FGF21 is mainly related to glucose homeostasis. CLINICALTRIALS.
GOV IDENTIFIER:
NCT01572090.
Journal:
INTERNATIONAL JOURNAL OF OBESITY
ISSN:
0307-0565
Year:
2016
Vol.:
40
N°:
9
pp.
1405 - 1415
Background/Objectives:Uroguanylin and guanylin are secreted by intestinal epithelial cells as prohormones postprandially and act on the hypothalamus to induce satiety. The impact of obesity and obesity-associated type 2 diabetes (T2D) on proguanylin and prouroguanylin expression/secretion as well as the potential role of guanylin and uroguanylin in the control of lipolysis in humans was evaluated.Subjects/Methods:Circulating and gastrointestinal expression of proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 134 subjects. In addition, plasma proguanylin and prouroguanylin were measured before and after weight loss achieved either by Roux-en-Y gastric bypass (RYGB) (n=24) or after a conventional diet (n=15). The effect of guanylin and uroguanylin (1¿100¿nmol¿l-1) on lipolysis was determined in vitro in omental adipocytes.Results:Circulating concentrations of prouroguanylin, but not proguanylin, were decreased in obesity in relation to adiposity. Weight loss achieved by RYGB increased plasma proguanylin and prouroguanylin. Obese T2D individuals showed higher expression of intestinal GUCA2A as well as of the receptors of the guanylin system, GUCY2C and GUCY2D, in omental adipocytes. The incubation with guanylin and uroguanylin significantly stimulated lipolysis in differentiated omental adipocytes, as evidenced by hormone-sensitive lipase phosphorylation at Ser563, an increase in fatty acids and glycerol release together with an upregulation of several lipolysis-related genes, including AQP3, AQP7, FATP1 or CD36.Conclusions:Both guanylin and uroguanylin trigger lipolysis in human visceral adipocytes. Given the lipolytic action of the guanylin system on visceral adipocytes, the herein reported decrease of circulating prouroguanylin concentrations in obese patients may have a role in excessive fat accumulation in obesity
Journal:
DIABETES
ISSN:
0012-1797
Year:
2016
Vol.:
65
N°:
12
pp.
3636 - 3648
Interleukin (IL)-32 is a recently described cytokine involved in the regulation of inflammation. We aimed to explore whether IL-32 could function as an inflammatory and angiogenic factor in human obesity and obesity-associated type 2 diabetes. Samples obtained from 90 subjects were used in the study. Obese patients exhibited higher expression levels of IL-32 in visceral adipose tissue (AT) as well as in subcutaneous AT and peripheral blood mononuclear cells. IL32 was mainly expressed by stromovascular fraction cells, and its expression was significantly enhanced by inflammatory stimuli and hypoxia, whereas no changes were found after the incubation with anti-inflammatory cytokines. The addition of exogenous IL-32 induced the expression of inflammation and extracellular matrix¿related genes in human adipocyte cultures, and IL32-silenced adipocytes showed a downregulation of inflammatory genes. Furthermore, adipocyte-conditioned media obtained from obese patients increased IL32 gene expression in human monocyte cultures, whereas the adipocyte-conditioned media from lean volunteers had no effect on IL32 mRNA levels. These findings provide evidence, for the first time, about the inflammatory and remodeling properties of IL-32 in AT, implicating this cytokine in obesity-associated comorbidities.
Journal:
PLOS ONE
ISSN:
1932-6203
Year:
2016
Vol.:
11
N°:
9
pp.
e0162189
To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics.
Journal:
ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN:
1137-6627
Year:
2016
Vol.:
39
N°:
1
pp.
23 - 33
Authors:
Sanchez-Santos, R.; Corcelles Codina, R.; Vilallonga Puy, R.; et al.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2016
Vol.:
26
N°:
12
pp.
2829 - 2836
Background Complications in sleeve gastrectomy (SG) can cast a shadow over the technique's good results and compromise its safety. The aim of this study is to identify risk factors for complications, and especially those that can potentially be modified to improve safety. Methods A retrospective multicenter cohort study was carried out, involving the participation of 29 hospitals. Data was collected on demographic variables, associated comorbidities, technical modifications, the surgeon's experience, and postoperative morbimortality. A multivariate logistic regression analysis was carried out on risk factors (RFs) for the complications of leak/fistula, hemoperitoneum, pneumonia, pulmonary embolism, and death. Results The following data were collected for 2882 patients: age, 43.85+/-11.6. 32.9 % male; BMI 47.22+/-8.79; 46.2 % hypertensive; 29.2 % diabetes2; 18.2 % smokers; bougie calibre >= 40 F 11.1 %; complications 11.7 % (2.8 % leaks, 2.7 % hemoperitoneum, 1.1 % pneumonia, 0.2 % pulmonary embolism); and death 0.6 %. RFs for complications were as follows: surgeon's experience < 20 patients, OR 1.72 (1.32-2.25); experience> 100 patients, OR 0.78 (0.69-0.87); DM2, OR1.48(1.12-1.95); probe > 40 F, OR 0.613 (0.429-0.876). Leak RFs were the following: smoking, OR1.93 (1.1-3.41); surgeon's experience< 20 patients, OR 2.4 (1.46-4.16); experience of 20-50 patients, OR 2.5 (1.3-4.86); experience > 100 patients, OR 0.265 (0.11-0.63); distance to pylorus > 4 cm, OR 0.510 (0.29-0.91). RFs for death were as follows: smoking, OR 8.64 (2.63-28.34); DM2, OR 3.25 (1.1-9.99); distance to pylorus< 5 cm, OR 6.62 (1.63-27.02). Conclusions The safety of SG may be compromised by nonmodifiable factors such as age > 65, patient comorbidities (DM2, hypertension), and prior treatment with anticoagulants, as well as by modifiable factors such as smoking, bougie size < 40 F, distance to the pylorus < 4 cm, and the surgeon's experience (< 50-100 cases).
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2016
Vol.:
26
N°:
7
pp.
1549-58
Background
Aging and obesity are two conditions associated with increased risk of cardiovascular disease. Our aim was to analyze whether an advanced age affects the beneficial effects of sleeve gastrectomy on weight loss and blood pressure in an experimental model of diet-induced obesity (DIO).
Methods
Young (6-month-old) and old (18-month-old) male Wistar DIO rats (n¿=¿101) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary interventions (pair-fed to the amount of food eaten by sleeve gastrectomized animals). Systolic (SBP), diastolic (DBP), and mean (MBP) blood pressure values and heart rate (HR) were recorded in conscious, resting animals by non-invasive tail-cuff plethysmography before and 4 weeks after surgical or dietary interventions.
Results
Aging was associated with higher (P¿<¿0.05) body weight and subcutaneous and perirenal fat mass as well as mild cardiac hypertrophy. Sleeve gastrectomy induced a reduction in body weight, whole-body adiposity, and serum total ghrelin in both young and old DIO rats. The younger group achieved a higher excess weight loss than the older group (164¿±¿60 vs. 82¿±¿17 %, P¿<¿0.05). A significant (P¿<¿0.05) decrease in insulin resistance, SBP, DBP, MBP, and HR without changes in heart weight was observed after sleeve gastrectomy independently of age.
Conclusion
Our results provide evidence for the effectiveness of sleeve gastrectomy without increased operative risk in body weight and blood pressure reduction
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2016
Vol.:
26
N°:
7
pp.
1537-48
Background: Susceptibility to obesity is associated with a notable inter-individual variation. The aim of the present study was to compare the effectiveness of sleeve gastrectomy (SG) on weight loss and metabolic profile in obesity-prone (OP) rats vs animals that are non-susceptible to obesity (NSO). Methods: Young male Wistar rats (n = 101) were put in a diet-induced obesity (DIO) programme with ad libitum access to a high-fed diet (HFD) during 12 months. Body weight and food intake were regularly registered. Thereafter, rats were ranked by final body weight to identify the obesity-prone (OP) (n = 13) and non-susceptible to obesity (NSO) (n = 14) animals. OP and NSO rats were submitted to surgical interventions (sham operation, SG and pair-fed to the amount of food eaten by sleeve-gastrectomized rats). Body weight, food intake, energy expenditure, body temperature, fat pads weight, and metabolic profiling were analysed 4 weeks after surgical or dietary interventions. Results: SG in both OP and NSO rats decreased body weight as compared to sham and pair-fed groups (P < 0.05), mainly due to reductions in subcutaneous and perirenal fat mass (P < 0.001). Total weight loss achieved in sleeve-gastrectomized OP and NSO rats was higher than that of pair-fed ones (P < 0.05), showing that the SG effect goes beyond caloric restriction. In this regard, sleeve-gastrectomized rats exhibited significantly (P < 0.05) increased basal rectal temperature together with upregulated brown adipose tissue Ucp-1 protein expression levels. A significant (P < 0.05) improvement in insulin sensitivity was also observed in both OP and NSO animals that underwent SG as compared with pair-fed counterparts. Conclusion: Our findings provide the first evidence that obesity-prone rats also benefit from surgery responding effectively to SG, as evidenced by the significant body weight reduction and the metabolic profile improvement.
Journal:
ENDOSCOPY
ISSN:
0013-726X
Year:
2016
Vol.:
48
N°:
Supl. 1
pp.
E346 - E347
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2015
Vol.:
25
N°:
9
pp.
1594-1603
The present study provides evidence for the existence of an adverse cardiometabolic profile in subjects currently considered to be outside traditional NIH guidelines but exhibiting a highly increased adiposity. It is concluded that body composition analysis yields valuable information to be incorporated into indication criteria for BS and that adiposity may be an independent indicator for BS.
Journal:
ACTA DIABETOLOGICA
ISSN:
0940-5429
Year:
2015
Vol.:
52
N°:
2
pp.
257-266
The ribosomal protein S6 kinase 1 (S6K1) is a component of the insulin signalling pathway that has been proposed as a key molecular factor in insulin resistance development under conditions of nutrient overload. The aim was to evaluate the involvement of S6K1 in obesity as well as to explore their association with visceral adipose tissue (VAT) inflammation. Samples obtained from 40 subjects were used. Gene expression levels of RPS6KB1 and key inflammatory markers were analysed in VAT. The effect of insulin on transcript levels of RPS6KB1 in human differentiated adipocytes was also explored. RPS6KB1 mRNA levels in VAT were increased (P < 0.05) in obese patients. Insulin treatment significantly enhanced (P < 0.01) gene expression levels of RPS6KB1 and a positive association (P < 0.05) of RPS6KB1 expression with different markers of insulin resistance was observed. Moreover, RPS6KB1 gene expression levels were positively correlated with VAT gene expression levels of the inflammatory markers CCL2, CD68, MMP2, MMP9, VEGFA and CHI3L1 as well as with mRNA levels of MTOR and MAPK8, representative players involved in signalling pathways related to S6K1. The increased levels of S6K1 in obesity and its positive association with insulin resistance and inflammation suggest a role for this protein in the changes that take place in VAT in obesity establishing a link between inflammation and a higher risk for the development of metabolic
Journal:
GENES AND NUTRITION
ISSN:
1555-8932
Year:
2015
Vol.:
10
N°:
3
pp.
460
Inflammation is a critical contributor to the pathogenesis of metabolic disorders with adipose tissue being crucial in the inflammatory response by releasing multiple adipokines with either pro- or anti-inflammatory activities with potential functions as metabolic regulators. Peripheral blood mononuclear cells (PBMC) have been proposed as representative of the inflammatory status in obesity. The aim of the present study was to evaluate the contribution of PBMC to the obesity-associated chronic inflammation analyzing the expression of novel adipokines. Samples obtained from 69 subjects were used in the study. Real-time PCR determinations were performed to quantify gene expression levels in PBMC of novel adipokines including chemerin, chitinase-3-like protein 1 (YKL-40), lipocalin-2 (LCN-2) and osteopontin (OPN), and their circulating concentrations were also determined by ELISA. We show, for the first time, that PBMC gene expression levels of chemerin (P < 0.0001), chitinase-3-like protein 1 (P = 0.010), lipocalin-2 (P < 0.0001) and osteopontin (P < 0.0001) were strongly upregulated in obesity independently of the glycemic state. Circulating concentrations of these adipokines followed the same trend being significantly higher (P < 0.05) in obese normoglycemic and type 2 diabetic patients compared to lean volunteers and also associated (P < 0.05) with their corresponding mRNA levels in PBMC. These results provide evidence that alterations in inflammation-related adipokines are
Journal:
GENES AND NUTRITION
ISSN:
1555-8932
Year:
2015
Vol.:
10
N°:
3
pp.
460
Inflammation is a critical contributor to the pathogenesis of metabolic disorders with adipose tissue being crucial in the inflammatory response by releasing multiple adipokines with either pro- or anti-inflammatory activities with potential functions as metabolic regulators. Peripheral blood mononuclear cells (PBMC) have been proposed as representative of the inflammatory status in obesity. The aim of the present study was to evaluate the contribution of PBMC to the obesity-associated chronic inflammation analyzing the expression of novel adipokines. Samples obtained from 69 subjects were used in the study. Real-time PCR determinations were performed to quantify gene expression levels in PBMC of novel adipokines including chemerin, chitinase-3-like protein 1 (YKL-40), lipocalin-2 (LCN-2) and osteopontin (OPN), and their circulating concentrations were also determined by ELISA. We show, for the first time, that PBMC gene expression levels of chemerin (P < 0.0001), chitinase-3-like protein 1 (P = 0.010), lipocalin-2 (P < 0.0001) and osteopontin (P < 0.0001) were strongly upregulated in obesity independently of the glycemic state. Circulating concentrations of these adipokines followed the same trend being significantly higher (P < 0.05) in obese normoglycemic and type 2 diabetic patients compared to lean volunteers and also associated (P < 0.05) with their corresponding mRNA levels in PBMC. These results provide evidence that alterations in inflammation-related adipokines are
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2015
Vol.:
25
N°:
9
pp.
1723 - 1734
BACKGROUND:
Glycerol constitutes an important metabolite for the control of lipid accumulation and glucose homeostasis. Our aim was to investigate the potential role of aquaglyceroporins, which are glycerol channels mediating glycerol efflux in adipocytes (AQP3 and AQP7) and glycerol influx (AQP9) in hepatocytes, in the improvement of adiposity and hepatic steatosis after sleeve gastrectomy in an experimental model of diet-induced obesity (DIO).
METHODS:
Male Wistar DIO rats (n = 161) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary interventions [fed ad libitum a normal diet (ND) or a high-fat diet (HFD) or pair-fed to the amount of food eaten by sleeve-gastrectomized animals]. The tissue distribution and expression of AQPs in biopsies of epididymal (EWAT) and subcutaneous (SCWAT) white adipose tissue and liver were analyzed by real-time PCR, Western blot, and immunohistochemistry.
RESULTS:
Four weeks after surgery, DIO rats undergoing sleeve gastrectomy showed a reduction in body weight, whole-body adiposity, and hepatic steatosis. DIO was associated with a tendency towards an increase in EWAT AQP3 and SCWAT AQP7 and a decrease in hepatic AQP9. Sleeve gastrectomy downregulated AQP7 in both fat depots and upregulated AQP3 in EWAT, without changing hepatic AQP9. Aqp7 transcript levels in EWAT and SCWAT were positively associated with adiposity and glycemia, while Aqp9 mRNA was negatively correlated with markers of hepatic steatosis and insulin resistance.
CONCLUSION:
Our results show, for the first time, that sleeve gastrectomy, a widely applied bariatric surgery procedure, restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, thereby improving whole-body adiposity and hepatic steatosis.
Journal:
ARCHIVES OF MEDICAL RESEARCH
ISSN:
0188-4409
Year:
2015
Vol.:
46
N°:
1
pp.
47-53
Increased STX8 expression in VAT appears to be associated with the presence of T2D in obese patients through a mechanism that may involve GLUT4.
Journal:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Year:
2014
Vol.:
99
N°:
8
pp.
E1407 - E1417
CONTEXT:
Wingless-type mouse mammary tumor virus integration site family (WNT)-5A is a glycoprotein involved in the regulation of the inflammatory response by activating the noncanonical Wnt signaling pathway. Secreted frizzled-related protein (SFRP)-5 acts as a decoy receptor that binds and sequesters WNT5A, preventing activation of frizzled receptors and attenuating the noncanonical Wnt signaling.
OBJECTIVE:
The aim of the study was to evaluate the involvement of WNT5A and SFRP5 in obesity and obesity-related comorbidities as well as to explore their effect in visceral adipose tissue inflammation.
PATIENTS AND METHODS:
Samples obtained from 90 subjects were used. Circulating and gene expression levels of WNT5A and SFRP5 were analyzed in different metabolic tissues. The effect of TNF-¿ and lipopolysaccharide on the transcript levels of WNT5A and SFRP5 in adipocytes was explored. We also investigated whether WNT5A itself can activate an inflammatory response.
RESULTS:
Increased circulating levels of WNT5A in obese patients (P < .05) were decreased (P < .001) after gastric bypass. In this line, WNT5A mRNA in visceral adipose tissue was increased (P < .05) in obese patients with gene expression levels of SFRP5 being down-regulated (P < .05). WNT5A mRNA expression was significantly enhanced (P < .01) by lipopolysaccharide and TNF-¿ treatment, whereas no effects were found in SFRP5 gene expression levels. Furthermore, exogenous WNT5A induced (P < .05) IL-6, IL1B, MMP2, MMP9, and SSP1 mRNA expression in human adipocyte cultures.
CONCLUSIONS:
Activation of noncanonical Wnt signaling through the up-regulation of WNT5A and down-regulation of SFRP5 may promote a proinflammatory state in visceral adipose tissue contributing to the development of obesity-associated comorbidities.
Journal:
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
ISSN:
0930-2794
Year:
2014
Vol.:
28
N°:
2
pp.
2412 - 2420
Background
Bariatric surgery (BS) has proven to be an effective treatment for morbid obesity. Osteopontin (OPN) is a proinflammatory cytokine involved in the development of obesity. The aim of our study was to determine the effect of weight loss following BS on circulating levels of OPN in humans.
Methods
Body composition and circulating concentrations of OPN and markers of bone metabolism were determined in obese patients who underwent Roux-en-Y gastric bypass (RYGB; n = 40) or sleeve gastrectomy (SG; n = 11).
Results
Patients who underwent RYGB or SG showed decreased body weight (P < 0.001) and body fat percentage (P < 0.001) as well as lower insulin resistance. However, plasma OPN levels were significantly increased after RYGB (P < 0.001) but remained unchanged following SG (P = 0.152). Patients who underwent RYGB also showed significantly increased C-terminal telopeptide of type-I collagen (ICTP) (P < 0.01) and osteocalcin (P < 0.001) while bone mineral density tended to decrease (P = 0.086). Moreover, OPN concentrations were positively correlated with the bone resorption marker ICTP after surgery. On the other hand, patients who underwent SG showed significantly increased ICTP levels (P < 0.05), and the change in OPN was positively correlated with the change in ICTP and negatively with the change in vitamin D after surgery (P < 0.05).
Conclusions
RYGB increased circulating OPN levels, while they remained unaltered after SG. The increase in OPN levels after RYGB could be related to the increased bone resorption in relation to its well-known effects on bone of this malabsorptive procedure in comparison to the merely restrictive SG.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2014
Vol.:
24
pp.
1702-1708
Circulating OPN levels decreased with HFD feeding remaining unaltered after SG. The expression of Spp1 in EWAT and liver was not modified by SG. The global improvement of metabolism after SG appears not to involve changes in serum OPN concentrations as well as in EWAT and liver expression in rats.
Journal:
CIRUGIA ESPAÑOLA
ISSN:
0009-739X
Year:
2014
Vol.:
92
N°:
2
pp.
143 - 144
Journal:
DIABETES CARE
ISSN:
0149-5992
Year:
2014
Vol.:
37
N°:
10
pp.
2813-2821
The current study provides evidence for the existence of a comparable adverse cardiometabolic profile in MHO and MAO patients; thus the MHO concept should be applied with caution. A better identification of the obesity phenotypes and a more precise diagnosis are needed for improving the management of obese individuals.
Journal:
INTERNATIONAL JOURNAL OF OBESITY
ISSN:
0307-0565
Year:
2014
Vol.:
38
N°:
9
pp.
1213 - 1220
Background/Objectives:Glycerol represents an important metabolite for the control of lipid accumulation and hepatic gluconeogenesis. We investigated whether hepatic expression and functionality of aquaporin-9 (AQP9), a channel mediating glycerol influx into hepatocytes, is impaired in non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in the context of insulin resistance.Subjects/Methods:Liver biopsies were obtained from 66 morbid obese patients undergoing bariatric surgery (66% women, mean body mass index (BMI) 46.1±1.0 kg m-2) with available liver echography and pathology analysis of the biopsies in this cross-sectional study. Subjects were classified according to normoglycemia (NG), impaired glucose tolerance (IGT) or type 2 diabetes (T2D). Hepatic expression of AQP9 was analyzed by real-time PCR, western blotting and immunohistochemistry, while glycerol permeability (P gly) was measured by stopped-flow light scattering.Results:AQP9 was the most abundantly (P<0.0001) expressed aquaglyceroporin in human liver (AQP9>>>AQP3>AQP7>AQP10). Obese patients with T2D showed increased plasma glycerol as well as lower P gly and hepatic AQP9 expression. The prevalence of NAFLD and NASH in T2D patients was 100 and 65%, respectively. Interestingly, AQP9 expression was decreased in patients with NAFLD and NASH as compared with those without hepatosteatosis, in direct relation to the degree of steatosis and lobular inflammation, being further reduced in insulin-resistant individuals. The association of AQP9 with insulin sensitivity was independent of BMI and age. Consistent with these data, fasting insulin and C-reactive protein contributed independently to 33.1% of the hepatic AQP9 mRNA expression variance after controlling for the effects of age and BMI.Conclusions:AQP9 downregulation together with the subsequent reduction in hepatic glycerol permeability in insulin-resistant states emerges as a compensatory mechanism whereby the liver counteracts further triacylglycerol accumulation within its parenchyma as well as reduces hepatic gluconeogenesis in patients with NAFLD.
Journal:
SURGERY FOR OBESITY AND RELATED DISEASES
ISSN:
1550-7289
Year:
2013
Vol.:
9
N°:
2
pp.
306-314
The increased levels of chemerin in obesity and its positive association with inflammation suggest a role for this chemoattractant protein in the changes that take place in visceral adipose tissue in the presence of energy surplus, establishing a link between inflammation and the greater risk of the development of metabolic disease.
Journal:
EUROPEAN JOURNAL OF NUTRITION
ISSN:
1436-6207
Year:
2013
Vol.:
52
N°:
6
pp.
1587-1595
These findings represent the first observation that STEAP4 and NGAL mRNA and protein levels in human VAT are related to iron status. Moreover, STEAP4 and NGAL are associated with pro-inflammatory markers suggesting their potential involvement in the low-grade chronic inflammation accompanying obesity.
Journal:
INTERNATIONAL JOURNAL OF OBESITY
ISSN:
0307-0565
Year:
2012
Vol.:
36
N°:
2
pp.
286 - 294
Journal:
DIABETES CARE
ISSN:
0149-5992
Year:
2012
Vol.:
35
N°:
2
pp.
383-88
CUN-BAE is an easy-to-apply predictive equation that may be used as a first screening tool in clinical practice. Furthermore, our equation may be a good tool for identifying patients at cardiovascular and type 2 diabetes risk.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2012
Vol.:
22
N°:
11
pp.
1786 - 1787
Journal:
Revista española de enfermedades digestivas
ISSN:
1130-0108
Year:
2012
Vol.:
104
N°:
6
pp.
326 - 329
La Consulta de Alto Riesgo de Tumores Digestivos tiene como objetivo fundamental identificar individuos con mayor riesgo de desarrollar tumores para hacer un diagnóstico presintomático de los mismos detectándolos en estadios en los que son potencialmente
Journal:
ENDOSCOPY
ISSN:
0013-726X
Year:
2012
Vol.:
44
N°:
Suppl. 2
pp.
UCTN:E366-7
Journal:
LIVER INTERNATIONAL
ISSN:
1478-3223
Year:
2012
Vol.:
32
N°:
6
pp.
951-61
The results suggest alterations in mitochondrial function and methionine metabolism as potential contributing factors to increased oxidative stress in liver of obese diabetic patients which may be influencing the development of NAFLD and NASH.
Journal:
Journal of Clinical Endocrinology & Obesity
ISSN:
0021-972X
Year:
2012
Vol.:
97
N°:
10
pp.
e1880 - e1889
Journal:
MEDICINA CLINICA
ISSN:
0025-7753
Year:
2012
Vol.:
139
N°:
1
pp.
44
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2012
Vol.:
104
N°:
8
pp.
436-439
the duodenal defect repair with a patch of the remant antrum, represents a valid alternative in similar circumstances. To our knowledge, it appears to be the first clinical description of this technique.
Journal:
ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN:
1137-6627
Year:
2012
Vol.:
35
N°:
3
pp.
433 - 444
Background. The prevalence of obesity in Spain in recent years has shown an alarming increase. The repeated failure of balanced food patterns, physical activity, nutritional education and pharmacotherapy have led to the need to use bariatric surgery both to maintain long-term weight loss, and for the resolution of associated comorbidities. This article analyzes the initial results of the implementation of the laparoscopic bariatric surgery program in Navarre, obtained in a group of obese patients with surgical indication and operated on by means of the laparoscopic gastric bypass. Methods. From January 2010 until December 2011, 47 gastric bypasses were performed laparoscopically in the University Clinic of Navarre, all of them from the autonomous community of Navarre and previously and subsequently evaluated in the Hospital Complex of Navarre. The first 19 cases amongst them were selected for this work, as they presented at least one year of follow-up. Results. The percentage of excess weight lost was 65.47%, with a 31.68% reduction of total weight. The figures for glucose, uric acid, arterial tension and lipid metabolism one year after the intervention presented a very significant progressive fall. No significant medical or surgical complications were presented. Conclusions. The laparoscopic gastric bypass is an efficient technique for the long-term treatment of morbid obesity, with a scant number of complications, excellent weight loss and curing or improvement of the associated comorbidities in these patients.
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2012
Vol.:
104
N°:
11
pp.
605 - 606
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2012
Vol.:
22
N°:
4
pp.
634 - 640
Background: Sleeve gastrectomy (SG) has been used as a multipurpose surgical procedure for the treatment of morbid obesity. The aim of the study was to analyze gastric morphology and histology at two different time points after SG in rats. Methods: Thirty-five male Wistar rats were fed ad libitum during 3 months on a high-fat diet to induce obesity. Subsequently, 25 diet-induced obese rats underwent either SG (n=12) or a sham operation (n=13). The remaining ten obese animals encompassed the nonoperated control group (Co). Four weeks postoperatively, 15 rats (n05 rats/experimental group) were sacrificed, while the remaining 20 rats were sacrificed after 16 weeks (animals/group; Co=5, sham=8, SG=7) to compare the gastric morphological and histopathological changes over time. Body weight and food intake were regularly recorded. Results: For both time periods, the Co groups exhibited the highest body weight, while the rats undergoing the SG showed the lowest weight gain (P<0.05). Initially, significant differences (P<0.005) in food intake relative to body weight were observed between the Co rats and animals undergoing surgery, which disappeared thereafter. The actual total stomach sizeafter both experimental periods in the SG group was similar to that of non- and sham-operated rats mainly due to a forestomach enlargement, which was more pronounced after 16 weeks. Traits of gastritis cystica profunda characterized by gastric foveolae elongation with hyperplasia and cystic dilatation of the glandswere observed in the residual stomachs of the sleeve-gastrectomized rats. These findings were mostly observed after 16 weeks of performing the SG, although they were also detected occasionally following 4 weeks postoperatively. No intestinal metaplasia was observed. Conclusion: After SG gastric macro- and microscopic changes with functional implications in both the short and long term take place.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2012
Vol.:
22
N°:
9
pp.
1481 - 1490
Sleeve gastrectomy constitutes an effective surgical procedure for the treatment of morbid obesity. The aim of the present study was to establish the effects of sleeve gastrectomy and caloric restriction on weight loss and cardiovascular parameters in diet-induced obese (DIO) rats.
Male Wistar DIO rats were subjected to surgical interventions (n = 30) (sham operation, sleeve gastrectomy, or pair-fed to the amount of food eaten by sleeve-gastrectomized animals and compared to lean control rats) or dietary interventions (n = 40) (fed ad libitum a normal diet (ND) or a high-fat diet or an ND with a caloric restriction of 25 %). Systolic blood pressure (SBP), diastolic blood pressure, and mean blood pressure values and heart rate (HR) were recorded in conscious, resting animals by noninvasive tail-cuff plethysmography before and 3 weeks after surgical or dietary interventions.
Both sleeve gastrectomy and caloric restriction induced a reduction in body weight, whole-body adiposity, and serum leptin together with an increased excess weight loss in DIO rats. Sleeve gastrectomy was further associated with an improvement in insulin resistance and the lipid profile, as well as with a reduction in serum ghrelin levels. A decrease in HR and heart weight was observed in caloric-restricted groups. Sleeve-gastrectomized rats not only exhibited a reduction in HR (a dagger HR = -45 +/- 19 bpm) but also in SBP values (a dagger SBP = -22 +/- 10 mmHg) compared to the DIO rats (a dagger SBP = 14 +/- 8 mmHg).
Our findings provide evidence that the beneficial effects of sleeve gastrectomy on blood pressure values are beyond weight loss in rats with diet-induced obesity.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2012
Vol.:
22
N°:
2
pp.
309-315
Sleeve gastrectomy constitutes an effective surgical procedure for the treatment of morbid obesity in humans and rodents with diet-induced obesity. The aim of the present study was to establish the effects of sleeve gastrectomy on weight loss and cardiovascular parameters in genetically obese (fa/fa) Zucker rats.
Eleven-week-old male obese (fa/fa) (n = 20) Zucker rats were assigned to three alternative procedures (sham operation, sleeve gastrectomy, or pair-fed to the amount of food eaten by sleeve-gastrectomized animals) and compared with lean Zucker (Fa/Fa) rats (n = 9). Systolic (SBP), diastolic (DBP), and mean (MBP) blood pressure values as well as heart rate (HR) were recorded in conscious, resting animals by non-invasive tail-cuff plethysmography before and 3 weeks after the surgical interventions.
Sleeve-gastrectomized rats experienced a reduction in body weight (P < 0.01), total adiposity amounts (P < 0.001), together with an increased excess weight loss (%EWL) (P < 0.05) compared with sham-operated and pair-fed animals 3 weeks after the surgical interventions. Rats with sleeve gastrectomy exhibited reduced (P < 0.01) blood pressure values (Delta SBP = -11 +/- 8 mmHg; Delta DBP = -6 +/- 4 mmHg; Delta MBP = -8 +/- 6 mmHg) compared with the control group, but no changes were observed in HR (P = 0.560). Sham-operated and pair-fed groups did not alter their cardiovascular variables.
Our findings provide evidence of the beneficial effects of sleeve gastrectomy on blood pressure values in addition to the weight loss in obese (fa/fa) Zucker rats independently of surgical trauma and food intake reduction.
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2012
Vol.:
104
N°:
11
pp.
605 - 606
Journal:
Diabetologia
ISSN:
0012-186X
Year:
2012
Vol.:
55
N°:
11
pp.
3038 - 3050
Journal:
OBESITY
ISSN:
1930-7381
Year:
2011
Vol.:
19
N°:
7
pp.
1439 - 1444
Journal:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Year:
2011
Vol.:
96
N°:
1
pp.
200 - 209
Journal:
MOLECULAR MEDICINE
ISSN:
1076-1551
Year:
2011
Vol.:
17
N°:
11-12
pp.
1157-67
Calprotectin has been recently described as a novel marker of obesity. The aim of this study was to determine the circulating concentrations and expression levels of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT), exploring its impact on insulin resistance and inflammation and the effect of weight loss. We included 53 subjects in the study. Gene expression levels of the S100A8/A9 complex were analyzed in VAT as well as in both adipocytes and stromovascular fraction cells (SVFCs). In addition, circulating calprotectin and soluble receptor for the advanced glycation end product (sRAGE) concentrations were measured before and after weight loss achieved by Roux-en-Y gastric bypass (RYGB) (n = 26). Circulating concentrations and VAT expression of S100A8/A9 complex were increased in normoglycemic and type 2 diabetic obese patients (P < 0.01) and associated with markers of inflammation (P < 0.01). Oppositely, concentrations of sRAGE were significantly lower (P < 0.001) in both obese groups compared to lean volunteers. Elevated calprotectin levels in obese patients decreased (P < 0.00001) after RYGB, whereas sRAGE concentrations tended to increase. Calprotectin was mainly expressed by SVFCs, and its expression was significantly correlated (P < 0.01) with mRNA levels of the monocyte-macrophage-related molecules macrophage-specific antigen CD68 (CD68), monocyte chemotactic protein 1 (MCP1), integrin ¿-M (CD11B), and NADPH oxidase 2 (NOX2). Tumor necrosis fac
Journal:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Year:
2011
Vol.:
96
N°:
4
pp.
586 - 597
Journal:
JOURNAL OF SURGICAL ONCOLOGY
ISSN:
0022-4790
Year:
2011
Vol.:
104
N°:
2
pp.
124-129
Background: Significant tumor downstaging has been achieved in patients with localized gastric adenocarcinoma by preoperative chemoradiotherapy (ChRT) or induction chemotherapy (Ch). However the influence of ChRT and Ch on postoperative outcomes has not yet been clarified, with very few studies examining this issue. We retrospectively analyzed the efficacy in terms of pathological response and early postoperative complications of two protocols of preoperative ChRT and Ch for locally advanced gastric cancer. Methods: Between 2000 and 2008, 72 patients with operable locally advanced gastric cancer (cT3-4/N+) were treated with preoperative treatment: 1-patients receiving induction Ch or 2-neoadjuvant Ch followed by concurrent ChRT. Postoperative histopathological regression and surgical complications were investigated including variables related to patients, surgical variables, preoperative treatment, and tumor. Results: There were no differences in the incidence of complications between the ChRT and Ch groups (30.9% vs. 33.3%). The most frequent complications were nonspecific surgical complications (pneumonia [12.5%] and infection from intravenous catheters [9.7%]). Risk factors for complications were high-body mass index (BMI > 25 kg/m(2)) and extension of surgery to the pancreas and spleen. A major pathological response was observed in 33.3% of patients, being more frequent in the ChRT group (47.6% vs. 13.3%; chi(2), P = 0.0024).
Journal:
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN:
0360-3016
Year:
2011
Vol.:
80
N°:
3
pp.
698-704
PURPOSE:
To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution.
METHODS AND MATERIALS:
From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment.
RESULTS:
Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%.
CONCLUSIONS:
The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.
Journal:
OBESITY SURGERY
ISSN:
0960-8923
Year:
2011
Vol.:
21
N°:
9
pp.
1438 - 1443
Background: Sleeve gastrectomy (SG) has been used for the surgical treatment of morbid obesity as a first or definitive procedure with satisfactory results. The objective of this study in rats was to establish the effects of SG on weight loss depending on the post-surgical type of diet followed. Methods: Thirty male Wistar rats were fed ad libitum during 3 months on a high-fat diet (HFD) to induce obesity. After this first phase, rats were subdivided in three groups of ten rats each and underwent a sham intervention, an SG, or no surgery but were pair-fed to the amount of food eaten by the animals of the SG group. At this time point, half of the animals in each group continued to be fed on the HFD, while the other half was switched to a normal chow diet (ND). Thus, the following subgroups were established: sham-ND, sleeve-ND, pair-fed-ND as well as sham-HFD, sleeve-HFD, and pair-fed-HFD. Body weight and food intake were recorded daily for 4 weeks. The feed efficiency rate (FER) was determined from weekly weight gains and caloric consumption during this period. Results: Statistically significant (P¿<¿0.05) differences in body weight were observed between the six experimental groups after 4 weeks of the interventions with rats in the sleeve-ND group experimenting the highest weight loss (-78.2¿±¿10.3 g) and animals in the pair-fed-HFD group exhibiting the lowest weight reduction (-4.0¿±¿0.1 g). Interestingly, the FER value of rats that underwent the SG and continued to be fed on a HFD was significantly (P¿<¿0.05) lower than that of sham operated and pair-fed animals on the same diet. Conclusion: The positive effects of SG on weight reduction are observed in obese rats submitted to the intervention and subsequently following an ND or even an HFD.
Journal:
CLINICAL AND TRANSLATIONAL ONCOLOGY
ISSN:
1699-048X
Year:
2011
Vol.:
13
N°:
12
pp.
899-903
OBJECTIVES Analysis of the results on the treatment of esophageal cancer by transthoracic esophagectomy by a multidisciplinary team of surgeons and oncologists. METHODS Between January 1990 and December 2009, 100 consecutive patients underwent transthoracic esophagectomy. Data were collected prospectively and clinical, pathological and histological features of the tumors were analyzed as well as the results of postoperative morbidity and mortality. RESULTS The average patient age was 55 years (range 31- 83 years). In 59 cases the tumor was located in the lower third and in 41 cases in the middle third. Forty-six patients had adenocarcinoma and 54 squamous cell carcinoma. In 54 cases radio-chemotherapy was planned preoperatively. Classifi cation according to pathological tumor stage was: stage 0 in 21 patients, stage I in 10 patients, stage IIa in 28, stage IIb in 9, stage III in 21 and stage IV in 11. The mean number of lymph nodes examined was 14 (range 0-28). Hospital mortality occurred in 4 cases and postoperative complications in 29 patients (33%). The most frequent postoperative complication was pulmonary complications in 17 cases. The average hospital stay was 15.2 days (range 10-40 days) CONCLUSIONS The results of esophageal cancer have been improved in recent years due to the formation of multidisciplinary teams in this pathology. In our study we have shown that the results obtained with the transthoracic technique for cancer of the esophagus are within the ranges rep
Journal:
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
ISSN:
0955-2863
Year:
2011
Vol.:
22
N°:
7
pp.
634 - 641
Journal:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Year:
2010
Vol.:
102
N°:
5
pp.
314 - 320
Background: intraductal papillary mucinous neoplasm (IPMN) shows a series of lesions which evolve from benign lesions -adenoma- to invasive carcinoma.
Aim: To analyze the clinical and pathological results of 15 patients diagnosed of IPMN, and surgically treated according to the guidelines of International Consensus Conference.
Material and methods: A retrospective analysis of 15 patients surgically treated between March 1993 and September 2009, according to the International Consensus recommendation. Demographic, diagnostic tools, surgical report, pathologic database and actuarial survival were analyzed with a follow-up from one and a half month through nine years.
Results: 6 Patients underwent pancreaticoduodenectomies, 4 total pancreatectomies, 2 body or central pancreatectomies, 2 partial pancreatectomies (enucleation) and 1 distal pancreatectomy. A morbidity of 46 and 0% hospital mortality were assessed, with a median length hospital stay of 10 days. In five cases, the IPMN was combined type (both main and branch pancreatic ducts involved) in four main duct-type and branch duct-type in the another six as well. Several atypia (IPMN carcinoma in situ) was observed in 2 patients and invasive carcinoma with negative lymph nodes was identified in 3 patients. A patient without invasive carcinoma died at 66 months of follow-up for pancreas adenocarcinoma. The actuarial survival up to recurrence or death was 105,133 months with a range of follow-up from 1 month and a half until 9 years.
Conclusions: IPMN main duct or mixed type warrants complete resection due to its incidence of invasive carcinoma or precursor lesions of malignancy as well. Due to its multifocal pattern, patients should be followed in long-term surveillance. The management of asymptomatic IPMN type branch less than 3 cm is controversial.
Journal:
TRANSPLANTATION PROCEEDINGS
ISSN:
0041-1345
Year:
2010
Vol.:
42
N°:
8
pp.
3079 - 3080
Diffuse thrombosis of the entire portal system (PVT) and cavernomatous transformation of the portal vein (CTPV) represents a demanding challenge in liver transplantation. We present the case of a patient with nodular regenerative hyperplasia and recurrent episodes of type B hepatic encephalopathy concomitant with PVT as well as CTPV, successfully treated with orthotopic liver transplantation. The portal inflow to the graft was carried out through the confluence of 2 thin paracholedochal varicose veins, obtaining good early graft function and recovery of the encephalopatic episodes. This alternative should be kept in mind as an option to assure hepatopetal splanchnic flow in those cases of diffuse thrombosis and cavernomatous transformation of portal vein.
Journal:
Revista española de enfermedades digestivas
ISSN:
1130-0108
Year:
2010
Vol.:
102
N°:
3
pp.
193 - 201
