Revistas
Revista:
EUROPEAN JOURNAL OF ENDOCRINOLOGY
ISSN:
0804-4643
Año:
2023
Vol.:
188
N°:
7
Págs.:
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.
Revista:
FRONTIERS IN IMMUNOLOGY
ISSN:
1664-3224
Año:
2023
Vol.:
14
Págs.:
1138316
Revista:
CANCERS
ISSN:
2072-6694
Año:
2023
Vol.:
15
N°:
4
Págs.:
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.
Autores:
Yárnoz-Esquiroz, P.; Olazarán, L.; Aguas-Ayesa, M.; et al.
Revista:
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN:
0014-2972
Año:
2022
Vol.:
52
N°:
7
Págs.:
e13811
Academic medicine fosters research that moves from discovery to translation, at the same time as promoting education of the next generation of professionals. In the field of obesity, the supposed integration of knowledge, discovery and translation research to clinical care is being particularly hampered. The classification of obesity based on the body mass index does not account for several subtypes of obesity. The lack of a universally shared definition of "obesities" makes it impossible to establish the real burden of the different obesity phenotypes. The individual's genotype, adipotype, enterotype and microbiota interplays with macronutrient intake, appetite, metabolism and thermogenesis. Further investigations based on the concept of differently diagnosed "obesities" are required.
Revista:
ACTA BIOMATERIALIA
ISSN:
1742-7061
Año:
2022
Vol.:
141
Págs.:
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.
Revista:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Año:
2022
Vol.:
23
N°:
16
Págs.:
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.
Revista:
METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN:
0026-0495
Año:
2022
Vol.:
128
Págs.:
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.
Autores:
Yarnoz-Esquiroz, P. (Autor de correspondencia); Chopitea, Ana; Olazarán, L.; et al.
Revista:
NUTRIENTS
ISSN:
2072-6643
Año:
2022
Vol.:
14
N°:
13
Págs.:
2754
Many studies have demonstrated that malnutrition has a negative impact on quality of life and mortality in patients with cancer. During the SARS-CoV-2 lockdown, dietary intake changes were detected in the Spanish population, reflecting an increase in the consumption of fruit, bread, flours, and eggs. The present study analyzed the nutritional status of 728 patients with cancer admitted once the SARS-CoV-2 lockdown finished, comparing it with the previous year as well as with mortality rates. The Malnutrition Universal Screening Tool (MUST) was applied in the first 24 h after admission. Age, gender, days of stay, circulating concentrations of albumin, cholesterol, C-reactive protein (CRP), lymphocytes, prealbumin, and mortality data were analyzed. Patients with cancer admitted between June and December of 2020 exhibited no statistical differences in BMI, age, or gender as compared to patients admitted in 2019. Statistically significant differences in nutritional status (p < 0.05), albumin (p < 0.001), and CRP (p = 0.005) levels regarding lockdown were observed in relation with a small non-significant reduction in mortality. In conclusion, following the SARS-CoV-2 lockdown, an improved nutritional status in cancer patients at admission was observed with a decrease in the percentage of weight loss and CRP levels together with an increase in albumin levels compared to oncological patients admitted the previous year.
Revista:
FRONTIERS IN IMMUNOLOGY
ISSN:
1664-3224
Año:
2022
Vol.:
13
Págs.:
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.
Revista:
NUTRIENTS
ISSN:
2072-6643
Año:
2022
Vol.:
14
N°:
20
Págs.:
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.
Revista:
JOURNAL OF INFLAMMATION RESEARCH
ISSN:
1178-7031
Año:
2022
Vol.:
15
Págs.:
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.
Revista:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Año:
2021
Vol.:
22
N°:
16
Págs.:
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.
Revista:
CELLULAR AND MOLECULAR IMMUNOLOGY
ISSN:
1672-7681
Año:
2021
Vol.:
18
N°:
10
Págs.:
2457 - 2459
Revista:
CELLULAR AND MOLECULAR IMMUNOLOGY
ISSN:
1672-7681
Año:
2021
Vol.:
18
N°:
4
Págs.:
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.
Revista:
NUTRIENTS
ISSN:
2072-6643
Año:
2021
Vol.:
13
N°:
4
Págs.:
1216
In children and adolescents, obesity does not seem to depend on a reduction of resting energy expenditure (REE). Moreover, in this young population, the interactions between either age and obesity or between age and gender, or the role of leptin on REE are not clearly understood. To compare the levels of REE in children and adolescents we studied 181 Caucasian individuals (62% girls) classified on the basis of age- and sex-specific body mass index (BMI) percentile as healthy weight (n = 50), with overweight (n = 34), or with obesity (n = 97) and in different age groups: 8-10 (n = 38), 11-13 (n = 50), and 14-17 years (n = 93). REE was measured by indirect calorimetry and body composition by air displacement plethysmography. Statistically significant differences in REE/fat-free mass (FFM) regarding obesity or gender were not observed. Absolute REE increases with age (p < 0.001), but REE/FFM decreases (p < 0.001) and there is an interaction between gender and age (p < 0.001) on absolute REE showing that the age-related increase is more marked in boys than in girls, in line with a higher FFM. Interestingly, the effect of obesity on absolute REE is not observed in the 8-10 year-old group, in which serum leptin concentrations correlate with the REE/FFM (r = 0.48; p = 0.011). In conclusion, REE/FFM is not affected by obesity or gender, while the effect of age on absolute REE is gender-dependent and leptin may influence the REE/FFM in 8-10 year-olds.
Revista:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN:
1422-0067
Año:
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.
Revista:
JOURNAL OF INFLAMMATION RESEARCH
ISSN:
1178-7031
Año:
2021
Vol.:
14
Págs.:
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.
Revista:
CELLS
ISSN:
2073-4409
Año:
2020
Vol.:
9
N°:
6
Págs.:
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.
Revista:
JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY
ISSN:
1018-9068
Año:
2020
Vol.:
30
N°:
5
Págs.:
367 - +
Revista:
JOURNAL OF INVESTIGATIONAL ALLERGOLOGY AND CLINICAL IMMUNOLOGY
ISSN:
1018-9068
Año:
2020
Vol.:
30
N°:
5
Págs.:
367 - 369
Revista:
JOURNAL OF CLINICAL MEDICINE
ISSN:
2077-0383
Año:
2020
Vol.:
9
N°:
4
Págs.:
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.
Autores:
Frühbeck, Gema; Fernandez-Quintana, B. ; Paniagua, M.; et al.
Revista:
METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN:
0026-0495
Año:
2020
Vol.:
108
Págs.:
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.
Revista:
OBESITY SURGERY
ISSN:
0960-8923
Año:
2020
Vol.:
30
N°:
11
Págs.:
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.
Revista:
ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN:
1137-6627
Año:
2020
Vol.:
43
N°:
3
Págs.:
435 - 437
Revista:
AGING-US
ISSN:
1945-4589
Año:
2019
Vol.:
11
N°:
6
Págs.:
1733 - 1744
Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor beta (TGF beta) superfamily which declines with age and exerts anti-aging regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting casting doubts about its true functional actions. The aim of the present study was to compare the circulating concentrations of GDF11 in individuals of different ages as well as body weight and glycemic status. Serum concentrations of GDF11 were measured by ELISA in 319 subjects. There was a significant increase in GDF11 concentrations in people in the 41-50 y group and a decline in the elder groups (61-70 and 71-80 y groups, P=0.008 for the comparison between all age groups). However, no significant correlation between fat-free mass index (FFMI), a formula used to estimate the amount of muscle mass in relation to height, and IogGDF11 was observed (r=0.08, P=0.197). Moreover, no significant differences in circulating concentrations of GDF11 regarding obesity or glycemic status were found. Serum GDF11 concentrations in humans decrease in older ages being unaltered in obesity and T2D. Further studies should determine the exact pathophysiological role of GDF11 in aging.
Revista:
JOURNAL OF CLINICAL MEDICINE
ISSN:
2077-0383
Año:
2019
Vol.:
8
N°:
6
Págs.:
878
Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor (TGF)-beta superfamily which declines with age and has been proposed as an anti-aging factor with regenerative effects in skeletal muscle in mice. However, recent data in humans and mice are conflicting, casting doubts about its true functional actions. The aim of the present study was to analyze the potential involvement of GFD11 in energy homeostasis in particular in relation with thyroid hormones. Serum concentrations of GDF11 were measured by enzyme-linked immunosorbent assay (ELISA) in 287 subjects. A highly significant positive correlation was found between GDF11 and thyroid-stimulating hormone (TSH) concentrations (r = 0.40, p < 0.001). Neither resting energy expenditure (REE) nor REE per unit of fat-free mass (REE/FFM) were significantly correlated (p > 0.05 for both) with GDF11 levels. In a multiple linear regression analysis, the model that best predicted logGDF11 included logTSH, leptin, body mass index (BMI), age, and C-reactive protein (logCRP). This model explained 37% of the total variability of logGDF11 concentrations (p < 0.001), with only logTSH being a significant predictor of logGDF11. After segregating subjects by TSH levels, those within the low TSH group exhibited significantly decreased (p < 0.05) GDF11 concentrations as compared to the normal TSH group or the high TSH group. A significant correlation of GDF11 levels with logCRP (r = 0.19, p = 0.025) was found. GDF11 levels were not related to the presence of hypertension or cardiopathy. In conclusion, our results show that circulating concentrations of GDF11 are closely associated with TSH concentrations and reduced in subjects with low TSH levels. However, GDF11 is not related to the regulation of energy expenditure. Our data also suggest that GDF11 may be involved in the regulation of inflammation, without relation to cardiac function. Further research is needed to elucidate the role of GDF11 in metabolism and its potential involvement in thyroid pathophysiology.
Revista:
JOURNAL OF TRANSLATIONAL MEDICINE
ISSN:
1479-5876
Año:
2019
Vol.:
17
Págs.:
48
Background and aims: Obesity is associated with impaired glucose tolerance which is a risk factor for cardiovascular risk. However, the oral glucose tolerance test (OGTT) is not usually performed in patients with normal fasting glycaemia, thus offering false reassurance to patients with overweight or obesity who may have post-prandial hyperglycaemia. As an alternative to resource demanding OGTTs, we aimed to examine the predictive value of anthropometric measures of total and central fat distribution for post-prandial hyperglycaemia in patients with overweight and obesity with normal fasting glycaemia enrolled in the DICAMANO study. Methods: We studied 447 subjects with overweight/obesity with a fasting glucose value <= 5.5 mmol l(-1) (99 mg dl(-1)) and BMI >= 25 kg/m(2) who underwent a 75-g OGTT. Post-prandial hyperglycaemia was defined as a glucose level >= 7.8 mmol l(-1) (140 mg dl(-1)) 2-h after the OGTT. The anthropometric measurements included body mass index, body adiposity index, waist circumference, neck circumference, waist-to-hip ratio and waist-to-height ratio. Results: The prevalence of post-prandial hyperglycaemia was 26%. Mean 1-h OGTT glucose levels, insulin resistance and beta cell dysfunction was higher in those subjects in the highest tertile for each anthropometric measurement, irrespective of fasting glucose level. Central fat depot anthropometric measurements were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. After multivariable-adjustment for fasting plasma glucose level, smoking, and physical activity level, the odds ratio (95% confidence intervals) for the presence of post-prandial hyperglycaemia for neck circumference, waist circumference and waist-to-height ratio were 3.3 (1.4, 7.7), 2.4 (1.4, 4.4) and 2.5 (1.4, 4.5), respectively. Conclusions: In this large and comprehensively phenotyped cohort, one in four subjects had post-prandial hyperglycaemia despite normal fasting glycaemia. Anthropometric indices of central fat distribution were strongly and independently associated with an increased risk of post-prandial hyperglycaemia. These results support the association between central adiposity and glucose derangements and demonstrate the clinical usefulness of anthropometric measurements as screening tools for the selection of patients who are most likely to benefit from an OGTT.
Revista:
JOURNAL OF CLINICAL MEDICINE
ISSN:
2077-0383
Año:
2019
Vol.:
8
N°:
4
Págs.:
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.
Revista:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Año:
2019
Vol.:
104
N°:
1
Págs.:
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.
Revista:
NUTRIENTS
ISSN:
2072-6643
Año:
2019
Vol.:
11
N°:
9
Págs.:
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.
Revista:
REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS
ISSN:
1130-0108
Año:
2019
Vol.:
111
N°:
5
Págs.:
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.
Revista:
ANNALES D ENDOCRINOLOGIE
ISSN:
0003-4266
Año:
2018
Vol.:
79
N°:
2
Págs.:
85 - 86
Revista:
CLINICAL NUTRITION
ISSN:
0261-5614
Año:
2018
Vol.:
37
N°:
2
Págs.:
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.
Revista:
OBESITY
ISSN:
1930-7381
Año:
2018
Vol.:
26
N°:
4
Págs.:
672 - 682
ObjectiveThe objective of this study was to assess the utility of the 2-hour oral glucose tolerance test (OGTT) value to discriminate between different cardiometabolic profiles and examine the role of body composition in predicting the associated increased risk for glucose impairment, beta-cell dysfunction, and cardiovascular disease (CVD). MethodsSubjects with normal fasting glucose completed a 2-hour OGTT and were categorized to the carbohydrate metabolism alterations (CMAs) or the control group based on a 2-hour glucose threshold of 7.8 mmol/L. Body composition, visceral adipose tissue, OGTT-based parameters, and cardiovascular risk factors (CVRFs) such as hypertension, dyslipidemia, obstructive sleep apnea, nonalcoholic fatty liver disease, and smoking status were measured. ResultsSubjects with CMAs exhibited a significantly higher 1-hour postload glucose level and a greater decline in beta-cell function and CVRF profiles. After multivariate adjustment, an excess of total body and visceral fat was associated with an increased risk of CMAs, beta-cell dysfunction, CVRFs, and lower whole-body insulin sensitivity. ConclusionsThese data support the etiopathogenic role of body and visceral fat in the development of glucose derangements and CVRFs early on in the metabolic dysregulation process. Thus, body composition analysis and OGTT assessment performed in individuals with normal fasting glucose enable a better identification of patients at risk of developing type 2 diabetes and CVD.
Revista:
METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN:
0026-0495
Año:
2018
Vol.:
87
Págs.:
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.
Revista:
INTERNATIONAL JOURNAL OF OBESITY
ISSN:
0307-0565
Año:
2017
Vol.:
41
N°:
9
Págs.:
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.
Revista:
ONCOIMMUNOLOGY
ISSN:
2162-402X
Año:
2017
Vol.:
6
N°:
7
Págs.:
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.
Revista:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Año:
2016
Vol.:
101
N°:
10
Págs.:
3803-3811
We conclude that serum ANGPTL8/betatrophin concentrations are altered in human dyslipidemia. ANGPTL8/betatrophin emerges as a potential player in dyslipidemia with a strong association with HDL-cholesterol and a potential therapeutic tool for the treatment of dyslipidemia.
Revista:
OBESITY SURGERY
ISSN:
0960-8923
Año:
2016
Vol.:
26
N°:
8
Págs.:
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.
Revista:
OBESITY SURGERY
ISSN:
0960-8923
Año:
2016
Vol.:
26
N°:
2
Págs.:
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.
Revista:
INTERNATIONAL JOURNAL OF OBESITY
ISSN:
0307-0565
Año:
2016
Vol.:
40
N°:
9
Págs.:
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
Revista:
DIABETES
ISSN:
0012-1797
Año:
2016
Vol.:
65
N°:
12
Págs.:
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.
Revista:
PLOS ONE
ISSN:
1932-6203
Año:
2016
Vol.:
11
N°:
9
Págs.:
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.
Revista:
ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN:
1137-6627
Año:
2016
Vol.:
39
N°:
1
Págs.:
23-33
Revista:
NUTRICION CLINICA Y DIETETICA HOSPITALARIA
ISSN:
0211-6057
Año:
2016
Vol.:
36
N°:
1
Págs.:
64-74
Revista:
OBESITY SURGERY
ISSN:
0960-8923
Año:
2015
Vol.:
25
N°:
9
Págs.:
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.
Revista:
GENES AND NUTRITION
ISSN:
1555-8932
Año:
2015
Vol.:
10
N°:
3
Págs.:
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
Revista:
GENES AND NUTRITION
ISSN:
1555-8932
Año:
2015
Vol.:
10
N°:
3
Págs.:
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
Revista:
ARCHIVES OF MEDICAL RESEARCH
ISSN:
0188-4409
Año:
2015
Vol.:
46
N°:
1
Págs.:
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.
Revista:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Año:
2014
Vol.:
99
N°:
8
Págs.:
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.
Revista:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Año:
2014
Vol.:
99
N°:
10
Págs.:
e2004-e2009
We conclude that serum betatrophin is decreased in human obesity, being further reduced in obesity-associated insulin resistance. Betatrophin levels are closely related to obesity-associated cardiometabolic risk factors, emerging as a potential biomarker of insulin resistance and T2D.
Revista:
DIABETES CARE
ISSN:
0149-5992
Año:
2014
Vol.:
37
N°:
10
Págs.:
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.
Revista:
INTERNATIONAL JOURNAL OF OBESITY
ISSN:
0307-0565
Año:
2014
Vol.:
38
N°:
9
Págs.:
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.
Revista:
SURGERY FOR OBESITY AND RELATED DISEASES
ISSN:
1550-7289
Año:
2013
Vol.:
9
N°:
2
Págs.:
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.
Revista:
JOURNAL OF CLINICAL SLEEP MEDICINE
ISSN:
1550-9389
Año:
2013
Vol.:
9
N°:
11
Págs.:
1165-71
Morbid obesity is frequently associated with abnormal LVM, particularly in patients with OSA; this association is independent of HT, BMI, body composition, and other clinical factors, supporting a direct role of OSA on LVM in morbid obesity. This suggests that OSA and LVM might be taken as predictors of the cardiovascular risk in these patients.
Revista:
EUROPEAN JOURNAL OF NUTRITION
ISSN:
1436-6207
Año:
2013
Vol.:
52
N°:
6
Págs.:
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.
Revista:
INTERNATIONAL JOURNAL OF OBESITY
ISSN:
0307-0565
Año:
2012
Vol.:
36
N°:
2
Págs.:
286 - 294
Revista:
DIABETES CARE
ISSN:
0149-5992
Año:
2012
Vol.:
35
N°:
2
Págs.:
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.
Revista:
LIVER INTERNATIONAL
ISSN:
1478-3223
Año:
2012
Vol.:
32
N°:
6
Págs.:
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.
Revista:
Journal of Clinical Endocrinology & Obesity
ISSN:
0021-972X
Año:
2012
Vol.:
97
N°:
10
Págs.:
e1880 - e1889
Revista:
ENDOSCOPY
ISSN:
0013-726X
Año:
2012
Vol.:
44
N°:
Supl. 2
Págs.:
E224
Revista:
Diabetologia
ISSN:
0012-186X
Año:
2012
Vol.:
55
N°:
11
Págs.:
3038 - 3050
Revista:
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
ISSN:
0939-4753
Año:
2011
Vol.:
21
N°:
4
Págs.:
245 - 253
Our work shows that NAMPT circulating concentrations and mRNA expression levels in PBC are increased in obese patients and that plasma NAMPT levels are related to inflammation, lipid metabolism and hepatic enzymes suggesting a potential involvement in fatty liver disease and in the obesity-associated inflammatory state.
Revista:
OBESITY
ISSN:
1930-7381
Año:
2011
Vol.:
19
N°:
7
Págs.:
1439 - 1444
Revista:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Año:
2011
Vol.:
96
N°:
1
Págs.:
200 - 209
Revista:
MOLECULAR MEDICINE
ISSN:
1076-1551
Año:
2011
Vol.:
17
N°:
11-12
Págs.:
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
Revista:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Año:
2011
Vol.:
96
N°:
4
Págs.:
586 - 597
Revista:
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
ISSN:
0955-2863
Año:
2011
Vol.:
22
N°:
7
Págs.:
634 - 641
Revista:
Journal of hypertension
ISSN:
0263-6352
Año:
2010
Vol.:
28
N°:
3
Págs.:
560 - 567
Objective The gut-derived hormone, ghrelin, improves cardiac function in healthy individuals and patients with chronic heart failure. The aim of this study was to investigate whether the major isoforms of the hormone, acylated and desacyl ghrelin, are related to inappropriate left ventricular mass in patients with the metabolic syndrome (MetS).
Methods and results Plasma concentrations of ghrelin forms were measured in 180 white participants (65 normal weight, 60 obese without MetS and 55 obese with MetS; 56% men). MetS was defined according to Adult Treatment Panel III criteria. The presence of left ventricular hypertrophy (LVH) was diagnosed by sex-specific left ventricular mass/height(2.7) cut-off values (> 49.2 g/m(2.7) for men and > 46.7 g/m(2.7) for women). Circulating concentrations of acylated ghrelin were increased in obesity and MetS, whereas desacyl ghrelin levels were decreased. Compared with participants in the lowest tertiles, the age-adjusted and sex-adjusted odds of having MetS were lower in the highest category of desacyl ghrelin (odds ratio 0.1, 95% confidence interval 0.1-0.4, P < 0.001). The prevalence of LVH was increased in the highest tertile of acylated ghrelin (odds ratio 3.4, 95% confidence interval 1.7-5.6, P < 0.05). Plasma acylated ghrelin was increased (P < 0.05) in patients with MetS exhibiting LVH compared with those with appropriate left ventricular mass, whereas plasma desacyl ghrelin was not changed (P = 0.490).
Conclusion Acylated ghrelin was positively associated with SBP and left ventricular mass indices, even after correction for BMI. These results suggest that the increased acylated ghrelin concentrations may represent a compensatory mechanism to overcome the development of hypertension and LVH in patients with MetS.
Revista:
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
ISSN:
0955-2863
Año:
2010
Vol.:
21
N°:
8
Págs.:
774 - 780
Adipose tissue is highly vascularized implying that angiogenesis takes place in its expansion. The aim of this study was to compare the concentrations of members of the vascular endothelial growth factor (VEGF) family in obesity. Serum concentrations of VEGFs were analyzed in 15 lean (BMI 20.3+/-2.5 kg/m(2)) and 24 obese (BMI 47.6+/-5.9 kg/m(2)) volunteers. Obese patients showed significantly increased circulating VEGF-A (150+/-104 vs. 296+/-160 pg/ml; P<.05), VEGF-B (2788+/-1038 vs. 4609+/-2202 arbitrary units; P<.05) and VEGF-C (13 453+/-5750 vs. 17 635+/-5117 pg/ml; P<.05) concentrations. Interestingly, levels of VEGF-D were reduced in obese individuals (538+/-301 vs. 270+/-122 pg/ml; P<.01). In addition, VEGF-A significantly decreased after weight loss following Roux-en-Y gastric bypass (BMI from 46.0+/-8.0 to 28.9+/-4.2 kg/m(2)P<.0001 vs. initial) from 345+/-229 to 290+/-216 pg/ml (P<.01). Moreover, in order to corroborate the human findings VEGF-A levels were analyzed during the expansion of adipose tissue in two dynamic models of murine obesity. Serum VEGF-A was significantly increased after 12 weeks on a high-fat diet (43.3+/-9.0 vs. 29.7+/-9.1 pg/ml; P<.01) or in ob/ob mice (52.2+/-18.0 vs. 29.2+/-7.7 pg/ml; P<.01) and was normalized after leptin replacement in the latter (32.4+/-14.0 pg/ml; P<.01 vs. untreated ob/ob). Our data indicates the involvement of these factors in the expansion of adipose tissue that takes place in obesity in relation to the need for increased vascularization, suggesting that manipulation of the VEGF system may represent a potential target for the pharmacological treatment of obesity.
Nacionales y Regionales
Título:
Papel de las adipo¿mioquinas en la susceptibilidad al desarrollo de COVID¿19 en la obesidad y diabetes tipo 2
Código de expediente:
0011-3638-2020-000002
Investigador principal:
Amaia Rodríguez Murueta-Goyena
Financiador:
GOBIERNO DE NAVARRA. DEPARTAMENTO DE SALUD
Convocatoria:
2020 GN Proyectos de Investigación en salud
Fecha de inicio:
21/12/2020
Fecha fin:
20/12/2021
Importe concedido:
34.999,10€
Otros fondos:
-
Título:
Medicina de precisión contra la diabetes Tipo 2: Predicción Genétcia e Intervención Nutricional con Probióticos moduladores de la Microbiota
Código de expediente:
CPP2021-008725
Investigador principal:
Pedro González Muniesa
Financiador:
AGENCIA ESTATAL DE INVESTIGACION
Convocatoria:
2021 AEI Proyectos en Colaboración Público Privada
Fecha de inicio:
01/03/2022
Fecha fin:
28/02/2025
Importe concedido:
403.500,08€
Otros fondos:
Fondos MRR
Título:
Cambios en la inflamación del tejido adiposo asociada a la obesidad y sus comorbilidades tras cirugía bariátrica inducidos por la
proteína 1 similar a la folistatina (FSTL1)
Código de expediente:
PI22/00745
Investigador principal:
Gema Frühbeck Martínez
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2022 AES Proyectos de investigación
Fecha de inicio:
01/01/2023
Fecha fin:
31/12/2025
Importe concedido:
232.320,00€
Otros fondos:
Fondos FEDER
Título:
Papel del inflamasoma en la regulación de la alteración de la barrera intestinal y la inflamación metabólica en un contexto de obesidad y diabetes tipo 2.
Código de expediente:
PI20/00927
Investigador principal:
Victoria Catalán Goñi
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2020 AES Proyectos de investigación
Fecha de inicio:
01/01/2021
Fecha fin:
31/12/2023
Importe concedido:
156.695,00€
Otros fondos:
Fondos FEDER
Título:
Papel de GDF15 en las alteraciones metabólicas relacionadas con la edad en el contexto de la obesidad.
Código de expediente:
PI20/00080
Investigador principal:
Javier Gómez Ambrosi
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2020 AES Proyectos de investigación
Fecha de inicio:
01/01/2021
Fecha fin:
31/12/2023
Importe concedido:
145.200,00€
Otros fondos:
Fondos FEDER
Título:
Implicación de neogenina 1 en la inflamación del tejido adiposo asociada a la obesidad y sus comorbilidades.
Código de expediente:
PI19/00785
Investigador principal:
Gema Frühbeck Martínez
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2019 AES Proyectos de investigación
Fecha de inicio:
01/01/2020
Fecha fin:
31/12/2022
Importe concedido:
284.652,50€
Otros fondos:
Fondos FEDER
Título:
Desarrollo de una ecuación (CUN-BAE2) para estimar el porcentaje de grasa corporal de adultos a partir del índice de masa corporal, la edad, el género y la actividad física.
Código de expediente:
DTS17/00174
Investigador principal:
Gema Frühbeck Martínez
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
AES 2017 DESARROLLO TECNOLÓGICO EN SALUD
Fecha de inicio:
01/01/2018
Fecha fin:
31/12/2019
Importe concedido:
33.550,00€
Otros fondos:
Fondos FEDER
Título:
Papel del inflamasoma en la regulación del inmunometabolismo, estrés oxidativo y remodelado de la matriz en la expansión del tejido adiposo asociada a la obesidad y sus comorbilidades.
Código de expediente:
PI17/02188
Investigador principal:
Victoria Catalán Goñi
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
AES2017 PROYECTOS DE INVESTIGACIÓN
Fecha de inicio:
01/01/2018
Fecha fin:
31/12/2020
Importe concedido:
110.715,00€
Otros fondos:
Fondos FEDER
Título:
Cambios en la plasticidad del tejido adiposo tras cirugía bariátrica y su papel en la mejoría de comorbilidades asociadas.
Código de expediente:
PI16/01217
Investigador principal:
Gema Frühbeck Martínez
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2016 AES PROYECTOS DE INVESTIGACIÓN
Fecha de inicio:
01/01/2017
Fecha fin:
31/12/2019
Importe concedido:
260.452,50€
Otros fondos:
Fondos FEDER