Nuestros investigadores

José Ignacio Monreal Marquiegui

Publicaciones científicas más recientes (desde 2010)

Autores: Recaredo, G.; Marin-Alejandre, B. A. ; Cantero, Irene; et al.
ISSN 2072-6643  Vol. 11  Nº 10  2019  págs. 2359
Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. Obesity and unhealthy dietary habits are described as risk factors for NAFLD. The aim of this study was to investigate the association between the consumption of different animal protein sources and hepatic status in NAFLD adults. A total of 112 overweight/obese participants with NAFLD from Fatty Liver in Obesity (FLiO) study were evaluated at baseline. Diet, body composition, and biochemical variables were evaluated. Hepatic status was also assessed by Magnetic Resonance Imaging, ultrasonography, and elastography. Red meat consumption showed a positive relationship with liver iron content (r = 0.224; p = 0.021) and ferritin concentration (r = 0.196; p = 0.037). Processed meat consumption exhibited a positive association with liver iron content (r = 0.308; p = 0.001), which was also found in the quantile regression (beta = 0.079; p = 0.028). Fish consumption was related with lower concentration of ferritin (r = -0.200; p = 0.034). This association was further evidenced in the regression model (beta = -0.720; p = 0.033). These findings suggest that the consumption of different animal protein sources differentially impact on liver status in obese subjects with NAFLD, showing fish consumption as a healthier alternative for towards NAFLD features.
Autores: Marín-Alejandre, B. A.; Abete, Itziar; Cantero, Irene; et al.
ISSN 2072-6643  Vol. 11  Nº 2  2019  págs. 322
The relevance of sleep patterns in the onset or evolution of nonalcoholic fatty liver disease (NAFLD) is still poorly understood. Our aim was to investigate the association between sleep characteristics and hepatic status indicators in obese people with NAFLD compared to normal weight non-NAFLD controls. Ninety-four overweight or obese patients with NAFLD and 40 non-NAFLD normal weight controls assessed by abdominal ultrasonography were enrolled. Hepatic status evaluation considered liver stiffness determined by Acoustic Radiation Force Impulse elastography (ARFI) and transaminases. Additionally, anthropometric measurements, clinical characteristics, and biochemical profiles were determined. Sleep features were evaluated using the Pittsburgh Sleep Quality Index (PSQI). Hepatic status parameters, anthropometric measurements, and clinical and biochemical markers differed significantly in NAFLD subjects compared to controls, as well as sleep efficiency, sleep disturbance score, and sleep quality score. In the NAFLD group, a higher prevalence of short sleep duration (p = 0.005) and poor sleep quality (p = 0.041) were found. Multivariate-adjusted odds ratio (95% confidence interval) for NAFLD considering sleep disturbance was 1.59 (1.11¿2.28). Regression models that included either sleep disturbance or sleep quality predicted up to 20.3% and 20.4% of the variability of liver stiffness, respectively, and after adjusting for potential confounders. Current findings suggest that sleep disruption may be contributing to the pathogenesis of NAFLD as well as the alteration of the liver may be affecting sleep patterns. Consequently, sleep characteristics may be added to the list of modifiable behaviors to consider in health promotion strategies and in the prevention and management of NAFLD.
Autores: Restituto, Patricia; et al.
ISSN 0300-0664  Vol. 91  Nº 3  2019  págs. 391 - 399
Context Bone loss is accelerated in the late perimenopause and early menopause. The date of the final menstrual period cannot be stated until 1 year after it has ended, and at that time, most of the rapid bone loss phase will have elapsed. Therefore, early detection of bone loss is crucial. Objectives To evaluate the utility of bone turnover markers (BTM) to identify the women who are more likely to lose more bone mass during the transition to menopause and quantify the loss of bone quality measured by trabecular bone score (TBS). Design, patients and setting Sixty-four healthy premenopausal women, mean age between 44 and 57 years old, were enrolled and followed up for 5 years. Clinical features, lifestyle, bone densitometry, TBS and BTM (CTX, P1NP and osteocalcin) were measured at baseline and follow-up. Results All women had densitometrically normal bone at the time of enrolment. After 5 years, 48.4% had normal bone mineral density, 45.8% low bone mass and 6.3% osteoporosis. Women with osteopenia/osteoporosis at follow-up had higher CTX and P1NP at enrolment compared with women with densitometrically normal bone. The areas under the curve for the prediction of low bone mass or osteoporosis were 0.69 (P = 0.011) for P1NP, 0.69 for CTX (P = 0.013) and 0.77 (P 0.001) for OC. A significant correlation was found between P1NP increase after 5 years and the decrease in lumbar bone density (r = -0.383, P = 0.002). At baseline, 7 (10.9%) women had deteriorated microarchitecture (TBS < 1.3). Three of these women developed osteoporosis and four osteopenia at follow-up. Conclusions Women with higher P1NP and CTX and lower TBS at baseline had lower BMD in the transition to menopause suggesting these novel tools could have potential use in identifying women at high risk of rapidly decreasing bone mass.
Autores: Izaguirre, Maitane; Gómez-Ambrosi, J; Rodríguez, Amaia; et al.
ISSN 2077-0383  Vol. 8  Nº 4  2019  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.
Autores: Cantero, Irene; Elorz, Mariana; Abete, Itziar; et al.
ISSN 1449-1907  Vol. 16  Nº 1  2019  págs. 75 - 83
Introduction: Non-alcoholic fatty liver disease (NAFLD) may progress to steatohepatitis, cirrhosis and complicated hepatocellular carcinoma with defined differential symptoms and manifestations. Objective: To evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging in adults subjects with non-alcoholic fatty liver disease. Materials and methods: A total of 127 overweight/obese with NAFLD, were parallelly assessed by Magnetic Resonance Imaging (MRI), ultrasonography, transient elastography and a validated metabolomic designed test to diagnose NAFLD in this cross-sectional study. Body composition (DXA), hepatic related biochemical measurements as well as the Fatty Liver Index (FLI) were evaluated. This study was registered as FLiO: Fatty Liver in Obesity study; NCT03183193. Results: The subjects with more severe liver disease were found to have worse metabolic parameters. Positive associations between MRI with inflammatory and insulin biomarkers were found. A linear regression model including ALT, RBP4 and HOMA-IR was able to explain 40.9% of the variability in fat content by MRI. In ROC analyses a combination panel formed of ALT, HOMA-IR and RBP4 followed by ultrasonography, ALT and metabolomic test showed the major predictive ability (77.3%, 74.6%, 74.3% and 71.1%, respectively) for liver fat content. Conclusions: A panel combination including routine blood markers linked to insulin resistance showed highest associations with MRI considered as a gold standard for determining liver fat content. This combination of tests can facilitate the diagnosis of early stages of non-alcoholic liver disease thereby avoiding other invasive and expensive methods.
Autores: Marin-Alejandre, B. A. ; Abete, Itziar; Cantero, Irene; et al.
ISSN 2072-6643  Vol. 11  Nº 10  2019  págs. 2543
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD management is mainly focused on weight loss, but the optimal characteristics of the diet demand further investigation. This study aims to evaluate the effects of two personalized energy-restricted diets on the liver status in overweight or obese subjects with NAFLD after a 6 months follow-up. Ninety-eight individuals from the Fatty Liver in Obesity (FLiO) study were randomized into two groups and followed different energy-restricted diets. Subjects were evaluated at baseline and after 6 months. Diet, anthropometry, body composition, and biochemical parameters were evaluated. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, and determination of transaminases. Both dietary groups significantly improved their metabolic and hepatic markers after the intervention, with no significant differences between them. Multivariate regression models evidenced a relationship between weight loss, adherence to the Mediterranean Diet (MedDiet), and a decrease in liver fat content, predicting up to 40.9% of its variability after 6 months. Moreover, the antioxidant capacity of the diet was inversely associated with liver fat content. Participants in the group with a higher adherence to the MedDiet showed a greater reduction in body weight, total fat mass, and hepatic fat. These results support the benefit of energy-restricted diets, high adherence to the MedDiet, and high antioxidant capacity of the diet for the management of NAFLD in individuals with overweight or obesity.
Autores: Vettorazzi, Ariane Renata, (Autor de correspondencia); Enciso, J. M.; et al.
ISSN 0278-6915  Vol. 111  2018  págs. 363 - 373
Ochratoxin A (OTA) is a potent renal carcinogen in male rats but not in females. The mechanisms underlying these differences are unknown. The sex-dependent response of F344 rats after a repeated OTA oral administration for 7 (0.50 mg/kg bw) or 21 days (0.21 and 0.50 mg/kg bw) was evaluated. General toxicity, sex and thyroid hormones and histopathology were studied. OTA was quantified (HPLC-FLD) in plasma, kidney and liver and the expression of kidney transporters (RT-qPCR) was studied. After 7 days, kidney histopathology showed more pronounced signs of toxicity in males than in females. After 21 days, a higher toxicity was observed but sex differences disappeared. OTA concentration in plasma and tissues was similar in both sexes. Downregulation was the general OTA-induced effect. Oats' downregulation was slow in males and Oat3 did not change in females. Oatp1 was strongly downregulated in males after 21 days. An opposite effect was observed in Bcrp after 21 days: downregulation in males and upregulation in females. Females showed a dose- and time-dependent decrease of progesterone. Despite the sex differences, the final balance in OTA toxicokinetics at renal cell level does not seem to support a higher accumulation of OTA in male kidneys.
Autores: Galarregui, C.; Zulet, María de los Ángeles; Cantero, Irene; et al.
ISSN 1422-0067  Vol. 19  Nº 11  2018  págs. 3662
Background: Dietary total antioxidant capacity (TAC), glycemic index (GI), and glycemic load (GL) are accepted indicators of diet quality, which have an effect on diet-disease relationships. The aim of this study was to evaluate potential associations of dietary TAC, GI, and GL with variables related to nutritive status and insulin resistance (IR) risk in cardiometabolic subjects. Methods: A total of 112 overweight or obese adults (age: 50.8 +/- 9 years old) were included in the trial. Dietary intake was assessed by a validated 137-item food frequency questionnaire (FFQ), which was also used to calculate the dietary TAC, GI, and GL. Anthropometrics, blood pressure, body composition by dual-energy X-ray absorptiometry (DXA), glycemic and lipid profiles, C-reactive protein (CRP), as well as fatty liver quantification by magnetic resonance imaging (MRI) were assessed. Results: Subjects with higher values of TAC had significantly lower circulating insulin concentration and homeostatic model assessment of insulin resistance (HOMA-IR). Participants with higher values of HOMA-IR showed significantly higher GI and GL. Correlation analyses showed relevant inverse associations of GI and GL with TAC. A regression model evidenced a relationship of HOMA-IR with TAC, GI, and GL. Conclusion: This data reinforces the concept that dietary TAC, GI, and GL are potential markers of diet quality, which have an impact on the susceptible population with a cardiometabolic risk profile.
Autores: Galarregui, C.; Abete, Itziar; Cantero, Irene; et al.
ISSN 0250-6807  Vol. 73  Nº Supl. 2  2018  págs. 30 - 30
Autores: Cantero, Irene; Abete, Itziar; Marin-Alejandre, A. ; et al.
ISSN 0250-6807  Vol. 73  Nº Supl 2  2018  págs. 45
Autores: Izaguirre, Maitane; Monreal, José Ignacio; et al.
ISSN 1534-4827  Vol. 6  Nº 43  2017 
Recent studies demonstrate that circulating levels of FGF19 are reduced in obesity. In fact, exogenous FGF19 administration is associated with a reduction in food intake as well as with improvements in glycaemia. In contrast, FGF21 levels are elevated in subjects with abdominal obesity, insulin resistance and T2D, probably representing a compensatory response. Additionally, elevated levels of circulating FGF23 in individuals with obesity and T2D are reported in most clinical studies. Finally, increased FGF1 levels in obese patients associated with adipogenesis have been described. FGFs constitute important molecules in the treatment of metabolic diseases due to their beneficial effects on glucose and lipid metabolism. Among all members, FGF19 and FGF21 have demonstrated the ability to improve glucose, lipid and energy homeostasis, along with FGF1, which was recently discovered to have beneficial effects on metabolic homeostasis. Additionally, FGF23 may also play a role in insulin resistance or energy homeostasis beyond mineral metabolism control. These results highlight the relevant use of FGFs as potential biomarkers for the early diagnosis of metabolic diseases. In this regard, notable progress has been made in the development of FGF-based therapies and different approaches are being tested in different clinical trials. However, further studies are needed to determine their potential therapeutic use in the treatment of obesity and obesity-related comorbidities
Autores: Cantero, Irene; Abete, Itziar; Monreal, José Ignacio; et al.
ISSN 2072-6643  Vol. 9  Nº 7  2017  págs. 667
he prevalence of non-alcoholic-fatty-liver-disease (NAFLD) is associated with obesity, diabetes, and metabolic syndrome (MS). This study aimed to evaluate the influence of two energy-restricted diets on non-invasive markers and scores of liver damage in obese individuals with features of MS after six months of follow-up and to assess the role of fiber content in metabolic outcomes. Seventy obese individuals from the RESMENA (Reduction of Metabolic Syndrome in Navarra) study were evaluated at baseline and after six months of energy-restricted nutritional intervention (American Heart Association (AHA) and RESMENA dietary groups). Dietary records, anthropometrical data, body composition by dual energy X-ray absorptiometry (DXA), and routine laboratory measurements were analyzed by standardized methods. Regarding liver status, cytokeratin-18 fragments and several non-invasive scores of fatty liver were also assessed. The RESMENA strategy was a good and complementary alternative to AHA for the treatment of obesity-related comorbidities. Participants with higher insoluble fiber consumption (¿7.5 g/day) showed improvements in fatty liver index (FLI), hepatic steatosis index (HIS), and NAFLD liver fat score (NAFLD_LFS), while gamma-glutamyl transferase (GGT) and transaminases evidenced significant improvements as a result of fruit fiber consumption (¿8.8 g/day). Remarkably, a regression model evidenced a relationship between liver status and fiber from fruits. These results support the design of dietary patterns based on the consumption of insoluble fiber and fiber from fruits in the context of energy restriction for the management of obese patients suffering fatty liver disease.
Autores: Murillo, Oihana; Moreno, Daniel; et al.
ISSN 1600-0641  Vol. 64  Nº 2  2016  págs. 419-26
Our data demonstrate that AAV8-AAT-ATP7B-mediated gene therapy provides long-term correction of copper metabolism in a clinically relevant animal model of WD providing support for future translational studies.
Autores: Restituto, Patricia; Monreal, José Ignacio; et al.
ISSN 0021-972X  Vol. 98  Nº 11  2013  págs. E1740 - E1748
Context: Bone turnover markers (BTMs) may identify changes in bone remodeling within a relatively short time interval before changes in bone mineral density can be detected. New markers such as osteoprotegerin, receptor activator of nuclear factor-B ligand, and sclerostin have emerged, but there is little information about their potential use in clinical practice. Design, Patients, and Setting: We performed an observational prospective study in pre-and postmenopausal ambulatory women (n =72 and n =152, respectively). Intervention: Postmenopausal women with osteoporosis (n =18) were treated with risedronate and calcium. Womenfilled out a questionnaire and underwent bone mineral density measurement using dual-energy x-ray absorptiometry at the time of enrollment and after 1 year of follow-up. BTMs were measured at baseline, at 6 months, and after 1 year. Results: Increased levels of N-terminal propeptide of type 1 procollagen (P1NP) and beta-type I collagen telopeptides (CTXs) were associated with low bone mineral density in the premenopausal (P =.02 and P =.04, respectively) and postmenopausal (P =.03 and P =.02) groups. The best analytical performance to diagnose osteoporosis was for = -CTX, osteocalcin, and P1NP, with areas under the curve of 0.70 (P =.005), 0.64 (P =.048), and 0.71 (P =.003). A significant decrease was found in P1NP, osteocalcin, tartrate-resistant acid phosphatase-5b, =-CTX, and bone alkaline phosphatase after 1 year of treatment (all P =.05). Conclusions: Our data suggest that measurement of beta beta-CTX and P1NP shows adequate analytical performance and could potentially be included in algorithms for the screening of osteoporosis. Furthermore, these two markers, along with osteocalcin and tartrate-resistant acid phosphatase5b, are useful to monitor the response to risedronate.
Autores: Vettorazzi, Ariane Renata; Wait, R.; Nagy, J.; et al.
ISSN 1756-0500  Vol. 6  2013  págs. 232 - 243
BACKGROUND: Androgen-dependent proteins (lipocalins) circulate in blood of male rats and mice and, being small (~ 18 kDa), pass freely into glomerular filtrate. Some are salvaged in proximal nephrons but some escape in urine. Several organic molecules can bind to these proteins causing, where salvage occurs, nephropathy including malignancy in renal cortex. In urine, both free lipocalins and ligands contribute to an increasingly-recognised vital biological role in social communication between adults, especially in the dark where reliance is on smell and taste. Crystal structure of the first-characterised lipocalin of male rats, alpha2u-globulin, has been determined and peptide sequences for others are available, but no study of occurrence during early puberty has been made. We have followed temporal occurrence in urine of juveniles (n = 3) for non-invasive pilot study by high resolution gradient mini-gel electrophoresis, tryptic digest of excised protein bands, and LC-MS/MS of digest to identify peptide fragments and assign to specific lipocalins. Study objective refers directly to external availability for social communication but also indirectly to indicate kinetics of circulating lipocalins to which some xenobiotics may bind and constitute determinants of renal disease. RESULTS: Mini-gels revealed greater lipocalin complexity than hitherto recognised, possibly reflecting post-translational modifications. Earliest patterns comprised rat urinary protein 1, already evident in Sprague-Dawley and Wistar strains at 36 and 52 days, respectively. By 44 and 57 days major rat protein (alpha2u-globulin) occurred as the progressively more dominant protein, though as two forms with different electrophoretic mobility, characterised by seven peptide sequences. No significant change in urinary testosterone had occurred in Wistars when major rat protein became evident, but testosterone surged by 107 days concomitant with the marked abundance of excreted lipocalins. CONCLUSIONS: Qualitative temporal changes in the composition of excreted lipocalins early in puberty, and apparent increase in major urinary protein as two resolvable forms, should catalyse systematic non-invasive study of urinary lipocalin and testosterone dynamics from early age, to illuminate this aspect of laboratory rodent social physiology. It could also define the potential temporal onset of nephrotoxic ligand risk, applicable to young animals used as toxicological models.
Autores: Salgado, Josefa; González, Álvaro; Alegre, Estíbaliz; et al.
Libro:  Principios de bioquímica clínica y patología molecular
2014  págs. 341-346
Complejo de glucoproteínas asociadas con la distrofina, distrofias musculares de Duchenne y Becker, técnicas bioquímicas diagnósticas de las distrofias musculares de Duchenne y Becker, otras distrofias.
Autores: González, Álvaro; Alegre, Estíbaliz; Monreal, José Ignacio; et al.
Libro:  Principios de bioquímica clínica y patología molecular
2014  págs. 347-353
Cadena respiratoria mitocondrial y fosforilación oxidativa, ADN mitocondrial, origen de las proteínas mitocondriales, alteraciones del ADN mitocondrial y envejecimiento, enfermedades mitocondriales o citopatías mitocondriales, estudio bioquímico general de las citopatías mitocondriales.
Autores: Salgado, Josefa; González, Álvaro; Alegre, Estíbaliz; et al.
Libro:  Principios de bioquímica clínica y patología molecular
2014  págs. 275 - 285
Desarrollo tumoral, marcadores tumorales, determinación de los marcadores tumorales, principales marcadores tumorales séricos, aplicación de los marcadores tumorales farmacogenómica y farmacogenética.
Autores: Navas-Carretero, Santiago; Monreal, José Ignacio;
Libro:  Fundamentos de nutrición y dietética : bases metodológicas y aplicaciones
2010  págs. 199 - 201