Daniel Del castillo - Academia.edu (original) (raw)

Papers by Daniel Del castillo

Research paper thumbnail of Expression of Jejunal Taste Receptors in Women with Morbid Obesity

Nutrients

Nutrient sensing plays important roles in promoting satiety and maintaining good homeostatic cont... more Nutrient sensing plays important roles in promoting satiety and maintaining good homeostatic control. Taste receptors (TAS) are located through the gastrointestinal tract, and recent studies have shown they have a relationship with metabolic disorders. The aim of this study was to analyze the jejunal expression of TAS1R2, TAS1R3, TAS2R14 and TAS2R38 in women with morbid obesity, first classified according to metabolic syndrome presence (MetS; n = 24) or absence (non-MetS; n = 45) and then classified according to hepatic histology as normal liver (n = 28) or nonalcoholic fatty liver disease (n = 41). Regarding MetS, we found decreased expression of TAS2R14 in MetS patients. However, when we subclassified patients according to liver histology, we did not find differences between groups. We found negative correlations between glucose levels, triglycerides and MetS with TAS1R3 expression. Moreover, TAS2R14 jejunal expression correlated negatively with the presence of MetS and ghrelin le...

Research paper thumbnail of External match loads imposed upon Ultimate Frisbee players: A comparison between playing positions

Science & Sports, 2021

Research paper thumbnail of Laparoscopic sleeve gastrectomy alters 1H-NMR-measured lipoprotein and glycoprotein profile in patients with severe obesity and nonalcoholic fatty liver disease

Scientific Reports, 2021

Patients with morbid obesity frequently present non-alcoholic fatty liver (NAFL) and non-alcoholi... more Patients with morbid obesity frequently present non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) associated with pro-atherogenic alterations. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for weight reduction, and for the remission of hepatic alterations. Using 1H-nuclear magnetic resonance (1H-NMR), we investigated the effects of LSG on lipoprotein and glycoprotein profile in patients with morbid obesity and liver disease. We included 154 patients with morbid obesity (49 non-NASH, 54 uncertain NASH, 51 definite NASH). A blood sample was obtained before surgery and, in patients with definite NASH, one year after surgery. Patients with NASH had increased concentrations of medium and small VLDL particles, VLDL and IDL cholesterol concentrations, IDL, LDL, and HDL triglyceride concentrations, and elevated glycoprotein levels. These changes were more marked in patients with type 2 diabetes mellitus. LSG produced significant decreases in the con...

Research paper thumbnail of Relationship between IL-8 Circulating Levels and TLR2 Hepatic Expression in Women with Morbid Obesity and Nonalcoholic Steatohepatitis

International Journal of Molecular Sciences, 2020

The progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH... more The progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is linked to systemic inflammation. Currently, two of the aspects that need further investigation are diagnosis and treatment of NASH. In this sense, the aim of this study was to assess the relationship between circulating levels of cytokines, hepatic expression of toll-like receptors (TLRs), and degrees of NAFLD, and to investigate whether these levels could serve as noninvasive biomarkers of NASH. The present study assessed plasma levels of cytokines in 29 normal-weight women and 82 women with morbid obesity (MO) (subclassified: normal liver (n = 29), simple steatosis (n = 32), and NASH (n = 21)). We used enzyme-linked immunosorbent assays (ELISAs) to quantify cytokine and TLR4 levels and RTqPCR to assess TLRs hepatic expression. IL-1β, IL-8, IL-10, TNF-α, tPAI-1, and MCP-1 levels were increased, and adiponectin levels were decreased in women with MO. IL-8 was significantly higher in...

Research paper thumbnail of Influence of opponent ranking on the physical demands encountered during Ultimate Frisbee match-play

Sports Biomechanics, 2020

There is a lack of evidence regarding the match demands encountered in elite Ultimate Frisbee (UF... more There is a lack of evidence regarding the match demands encountered in elite Ultimate Frisbee (UF) overall and dependent upon opponent ranking. These data may be useful to elite UF coaches to implement optimal training loads and recovery strategies. Therefore, this study quantified the physical demands of elite UF match-play and analysed differences in demands according to opponent ranking. Twelve UF players from the same national team participated in the study. An observational design was used to compare the physical demands encountered by players between opponents carrying different rankings (1st, 3rd, 4th, and 5th) during four official matches in a 5-team competition. No significant differences (p > 0.05) in sprinting and repeated-sprinting activity were evident across UF matches between opponents. In contrast, a higher (moderate-large) quantity and greater intensities of body impacts were observed in UF matches played against higher-ranked (1st) compared to lower-ranked teams (3rd, 4th, and 5th). Additionally, greater (moderate-large) PL and metabolic power were observed in matches played against higher-ranked (1st) compared to lower-ranked teams (3rd and 4th). These findings suggest coaches may need to reduce the training loads in the next days after the matches played against higher-ranked opponents compared to when facing lower-ranked opponents.

Research paper thumbnail of Plasma metabolic alterations in patients with severe obesity and non-alcoholic steatohepatitis

Alimentary Pharmacology & Therapeutics, 2019

Background: Obesity can influence hepatic mitochondrial function, and cause nonalcoholic steatohe... more Background: Obesity can influence hepatic mitochondrial function, and cause nonalcoholic steatohepatitis (NASH). Diagnosis and follow-up rely on invasive liver biopsy so blood-based markers are urgently required. Aim: To investigate whether values of circulating metabolites from energy and onecarbon (1-C) metabolism may: (a) reflect hepatic mitochondrial flexibility failure and (b) act as NASH biomarkers. Methods: Patients with severe obesity undergoing bariatric surgery (n = 270) were investigated using quantitative targeted plasma metabolomics. Comparisons were with non-obese controls without liver disease (n = 50). Obese patients with NASH (n = 53) and without NASH (n = 130) representing extreme groups of liver disease were assessed to test the diagnostic ability of the measured circulating metabolites. Paired liver biopsy and plasma samples from NASH patients were available 1 year post-surgery and were evaluated to monitor metabolomic changes with liver damage resolution. Results: We identified correlations between human liver metabolism and obesity. High-plasma α-ketoglutarate (α-KG) and lactate concentrations in NASH patients indicating citric acid cycle replenishment via glutaminolysis might also be a crucial point in NASH onset. Plasma measurements of α-KG, β-hydroxybutyrate, pyruvate and oxaloacetate reduced the uncertainty in clinical diagnosis of NASH [area under receiver operating characteristic curve (AUC) of 0.826] and predicted NASH resolution without ambiguity (AUC of 0.999). Conclusion: Changes in plasma mitochondrial metabolites appear to be associated with NASH. These metabolic responses may be dynamically remodelled following resolution of liver damage through massive weight loss.

Research paper thumbnail of Low Circulating Levels of Neurotensin in Women with Nonalcoholic Fatty Liver Disease Associated with Severe Obesity

Obesity (Silver Spring, Md.), Feb 25, 2017

This study was performed to investigate neurotensin plasma levels in patients with nonalcoholic f... more This study was performed to investigate neurotensin plasma levels in patients with nonalcoholic fatty liver disease (NAFLD) associated with severe obesity. The plasma levels of neurotensin in 20 women with normal weight and 51 women with morbid obesity (MO) were measured, and women were subclassified according to their hepatic histology as having MO without NAFLD (n = 18) or MO with NAFLD (n = 33). The NAFLD group included 15 women with simple steatosis (SS) and 18 women with nonalcoholic steatohepatitis (NASH). To quantify neurotensin in plasma, a multiplex sandwich immunoassay with a Luminex magnetic bead-based platform was used. Neurotensin levels were significantly decreased (P = 0.001) in women with MO and NAFLD (3.62 ± 0.85 ng/mL), compared with women with MO and normal liver function (11.65 ± 1.95 ng/mL; P = 0.001) and women with normal weight (13.68 ± 2.58 ng/mL; P = 0.001). There was no difference in levels between women with SS and women with NASH (P = 0.415). Circulating ...

Research paper thumbnail of Hepcidin in morbidly obese women with non-alcoholic fatty liver disease

PloS one, 2017

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in We... more Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Both iron and lipid metabolism seem to be involved in its pathogenesis. We aimed to assess the relationship between levels of hepcidin, the master iron-regulatory protein, in plasma and the presence of NAFLD in morbidly obese (MO) patients, and to investigate the association between the hepatic expression of the main iron and lipid metabolism -related genes. Enzyme-linked immunosorbent assay was used to measure plasma hepcidin levels in 49 normal-weight control women, 23 MO women with normal liver (NL) histology and 46 MO women with NAFLD. The mRNA expression of hepcidin, the main iron metabolism-related genes, and the main lipid-metabolism genes was quantified by qRT-PCR in liver biopsies from members of the MO group undergoing bariatric surgery. Circulating hepcidin levels were significantly greater in MO than in normal-weight control women. However, there were no sign...

Research paper thumbnail of miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease

International Journal of Molecular Sciences, 2016

Specific miRNA expression profiles have been shown to be associated with nonalcoholic fatty liver... more Specific miRNA expression profiles have been shown to be associated with nonalcoholic fatty liver disease (NAFLD). We examined the correlation between the circulating levels and hepatic expression of miR122 and miR33a/b*, the key lipid metabolism-related gene expression and the clinicopathological factors of obese women with NAFLD. We measured miR122 and miR33a/b* expression in liver samples from 62 morbidly obese (MO), 30 moderately obese (ModO), and eight normal-weight controls. MiR122 and miR33a/b* expression was analyzed by qRT-PCR. Additionally, miR122 and miR33b* circulating levels were analyzed in 122 women. Hepatic miR33b* expression was increased in MO compared to ModO and controls, whereas miR122 expression was decreased in the MO group compared to ModO. In obese cohorts, miR33b* expression was increased in nonalcoholic steatohepatitis (NASH). Regarding circulating levels, MO patients with NASH showed higher miR122 levels than MO with simple steatosis (SS). These circulating levels are good predictors of histological features associated with disease severity. MO is associated with altered hepatic miRNA expression. In obese women, higher miR33b* liver expression is associated with NASH. Moreover, multiple correlations between miRNAs and the expression of genes related to lipid metabolism were found, that would suggest a miRNA-host gene circuit. Finally, miR122 circulating levels could be included in a panel of different biomarkers to improve accuracy in the non-invasive diagnosis of NASH.

Research paper thumbnail of Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

PloS one, 2016

Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from si... more Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS) and steatohepatitis (NASH) cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients. We used a gas chromatography-quadruple time-of-flight-mass spectrometry analysis to quantify alpha-ketoglutarate in serum from normal-weight subjects (n = 30) and morbidly obese women (n = 97) with or without NAFLD. We found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, ...

Research paper thumbnail of Downregulation of de Novo Fatty Acid Synthesis in Subcutaneous Adipose Tissue of Moderately Obese Women

International Journal of Molecular Sciences, 2015

The purpose of this work was to evaluate the expression of fatty acid metabolism-related genes in... more The purpose of this work was to evaluate the expression of fatty acid metabolism-related genes in human adipose tissue from moderately obese women. We used qRT-PCR and Western Blot to analyze visceral (VAT) and subcutaneous (SAT) adipose tissue mRNA expression involved in de novo fatty acid synthesis (ACC1, FAS), fatty acid oxidation (PPARα, PPARδ) and inflammation (IL6, TNFα), in normal weight control women (BMI < 25 kg/m 2 , n = 35) and moderately obese women (BMI 30-38 kg/m 2 , n = 55). In SAT, ACC1, FAS and PPARα mRNA expression were significantly decreased in moderately obese women compared to controls. The downregulation reported in SAT was more pronounced when BMI increased. In VAT, lipogenic-related genes and PPARα were similar in both groups. Only PPARδ gene expression was significantly increased in moderately obese women. As far as inflammation is concerned, TNFα and IL6 were significantly increased in moderate obesity in both tissues. Our results indicate that there is a progressive downregulation in lipogenesis in SAT as BMI increases, which suggests that SAT decreases the synthesis of fatty acid de novo during the development of obesity, whereas in VAT lipogenesis remains active regardless of the degree of obesity.

Research paper thumbnail of Cirugía experimental y obesidad mórbida

Research paper thumbnail of Tissue-specific DNA methylation profiles regulate liver-specific expression of the APOA1/C3/A4/A5 cluster and can be manipulated with demethylating agents on intestinal cells

Atherosclerosis, 2014

Objective: The tissue-specific expression profiles of genes within the APOA1/C3/A4/A5 cluster pla... more Objective: The tissue-specific expression profiles of genes within the APOA1/C3/A4/A5 cluster play an important role in lipid metabolism regulation. We hypothesize that the tissue-specific expression of the APOA1/C3/A4/A5 gene cluster will show an inverse pattern with DNA methylation, and that repression in non-or low-expressing tissue, such as the intestine, can be reversed using epigenetic drugs. Methods and results: We analyzed DNA samples from different human adult tissues (liver, intestine, leukocytes, brain, kidney, pancreas, muscle and sperm) using the Infinium HumanMethyation450 BeadChip array. DNA methylation profiles in APOA1/C3/A4/A5 gene cluster were confirmed by bisulfite PCR and pyrosequencing. To determine whether the observed tissue-specific methylation was associated with the expression profile we exposed intestinal TC7/Caco-2 cells to the demethylating agent 5-Aza-2 0-deoxycytidine and monitored intestinal APOA1/C3/A4/A5 transcript re-expression by RT-qPCR. The promoters of APOA1, APOC3 and APOA5 genes were less methylated in liver compared to other tissues, and APOA4 gene was highly methylated in most tissues and partially methylated in liver and intestine. In TC7/Caco-2 cells, 5-Aza-2 0-deoxycytidine treatment induced a decrease between 37 and 24% in the methylation levels of APOA1/C3/A4/A5 genes and a concomitant re-expression mainly in APOA1, APOA4 and APOA5 genes ranging from 22 to 600%. Conclusions: We have determined the methylation patterns of the APOA1/C3/ A4/A5 cluster that may be directly involved in the transcriptional regulation of this cluster. DNA demethylation of intestinal cells increases the RNA levels especially of APOA1, APOA4 and APOA5 genes.

Research paper thumbnail of Endocannabinoid Receptors Gene Expression in Morbidly Obese Women with Nonalcoholic Fatty Liver Disease

BioMed Research International, 2014

Background. Recent reports suggest a role for the endocannabinoid system in the pathology of nona... more Background. Recent reports suggest a role for the endocannabinoid system in the pathology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between liver expression of cannabinoid (CB) receptor subtypes, CB1 and CB2, in morbidly obese (MO) women with different histological stages of NAFLD.Methods. We analysed hepatic CB1 and CB2 mRNA expression, and the expression of genes involved in lipid metabolism in 72 MO women, subclassified by liver histology into MO with normal liver (NL,n=16), simple steatosis (SS,n=28), and nonalcoholic steatohepatitis (NASH,n=28) by enzyme-linked immunosorbent assay and RT-PCR.Results. We found that CB1 mRNA expression was significantly higher in NASH compared with SS and correlated negatively with PPARα. Regarding CB2, CB2 mRNA expression correlated positively with ACC1, PPARγ, IL6, TNFα, resistin, and adiponectin.Conclusions. The increased expression of CB1 in NASH and the negative correlation with PP...

Research paper thumbnail of Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

International Journal of Molecular Sciences, 2014

Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the... more Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in

Research paper thumbnail of Retinol binding protein-4 circulating levels were higher in nonalcoholic fatty liver disease vs. histologically normal liver from morbidly obese women

Obesity, 2013

nature publishing group articles Genetics IntroductIon Nonalcoholic fatty liver disease (NAFLD) h... more nature publishing group articles Genetics IntroductIon Nonalcoholic fatty liver disease (NAFLD) has frequently been associated with obesity, type 2 diabetes mellitus (T2DM), hyperlipidemia, and insulin resistance, which are the main features of metabolic syndrome (1,2). NAFLD is an increasingly recognized condition that has become the most common liver disorder in the developed world (1). NAFLD causes a wide spectrum of liver damage, ranging from simple steatosis (SS) to cirrhosis. In most cases, SS does not progress to a more severe disease, but ~20-30% of patients have histological signs of fibrosis and necroinflammation, indicating a presence of nonalcoholic steatohepatitis (NASH) (3). The pathogenesis of NAFLD is poorly understood and much of the current opinion remains hypothetical. Obesity is considered an important risk factor, though not all patients with NAFLD are obese (4). In obesity, an altered secretion of proteins takes place in the adipose tissue, the so-called adipokines, which have wide-ranging endocrine and paracrine effects on general metabolism (5). These adipokines are considered important determinants of obesity-related disorders such as insulin resistance, inflammation, and dyslipidemia (6). Consequently, there is growing evidence that adipokines are one of the causal links between obesity and NAFLD (7). A recently identified adipokine is the retinol binding protein-4 (RBP4), the specific carrier protein of retinol (vitamin A) in the blood. Although the major tissue site of RBP4 synthesis in the body is the liver, other sites of synthesis have been reported such as adipose tissues, kidney, and brain (8-10). It has been put forward that adipose tissue in humans, as occurs in mice, has the second highest level of RBP4 expression (8). Circulating RBP4 levels have been associated with estimations of adiposity and insulin resistance (11-13). Interestingly, we and others have reported a downregulation of RBP4 messenger RNA (mRNA) in subcutaneous adipose tissue (SAT)

Research paper thumbnail of Clinical and adipocytokine changes after bariatric surgery in morbidly obese women

Obesity, 2013

Objective: Recent studies report the effect of bariatric surgery on glycaemia control and prevent... more Objective: Recent studies report the effect of bariatric surgery on glycaemia control and prevention of type-2-diabetes in obese patients. This study is about the pathophysiological mechanisms associated to these changes. Design and Methods: Circulating levels of receptors of tumor necrosis factor (TNF-RI, TNF-RII), visfatin, high molecular weight (HMW) adiponectin, and C reactive protein (CRP) in 30 morbidly obese women (body mass index, BMI>40 kg/m 2) and 60 normal-weight controls (BMI>25 kg/m 2) were analyzed. Morbidly obese were studied at three time-points: before surgery (baseline), and 6 and 12 months after. Results: After surgery, the levels of TNF-RI, TNF-RII, visfatin, and CRP were significantly lower than its baseline levels, whereas HMW adiponectin was higher. Fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA2-IR) levels were markedly lower postoperatively. High density lipoproteins (HDL) moderately increased, and triglyceride levels had sharply decreased. The study of the predictive value of variables indicated that preoperative levels of TNF-RI and visfatin correlated positively with levels of glucose, insulin, glycosylated hemoglobin A1c, and HOMA2-IR postoperatively, whereas adiponectin levels correlated negatively. Baseline CRP levels negatively linked to HDL and TNF-RII positively to triglyceride. Conclusions: The preoperative profile with high levels of proinflammatory adipocytokines is linked to smaller improvements in glucose homeostasis and lipid factors. The use of a range of biomarkers may predict the level of metabolic changes following bariatric surgery.

Research paper thumbnail of Inhibition of hepatic cell nuclear DNA fragmentation by zinc in carbon tetrachloride-treated rats

Journal of Hepatology, 1999

Background/Aims: The aims of this study were to ascertain: 1) whether hepatic cell DNA fragmentat... more Background/Aims: The aims of this study were to ascertain: 1) whether hepatic cell DNA fragmentation is increased in rats with early stages of liver disease induced by carbon tetrachloride; 2) whether the inhibition of DNA cleavage is involved in the hepatoprotective effects of zinc; and 3) if relationships exist between DNA fragmentation and the onset of fibrosis in this experimental model. Methods: Twenty-one treated rats and 23 controls were divided into two groups to receive either a standard diet or one supplemented with zinc. All the animals were sacrificed 1 week later for histological and biochemical assessments, which included a DNA fragmentation index, hepatic zinc and metallothionein concentrations, fibrosis measured by hepatic hydroxyproline concentration and plasma alanine aminotransferase activity. Results: Hepatic cell DNA fragmentation was in-T   an increasing body of evidence, from human and experimental studies, suggesting that zinc could be a beneficial agent in the protection against hepatotoxicity (1,2). A close association was found between low serum zinc content and fibrogenesis in patients with alcoholic liver disease (3). Additionally, studies in a model of cirrhosis, experimentally induced in the rat by chronic carbon tetrachloride administration, indicated that zinc supplementation decreased hepatic collagen content and fibrogenesis, activated collagenolytic enzymes and limited the pro

Research paper thumbnail of Plasma visfatin levels and gene expression in morbidly obese women with associated fatty liver disease

Clinical Biochemistry, 2013

The few studies on the physiopathological role of visfatin in morbid obesity and the related meta... more The few studies on the physiopathological role of visfatin in morbid obesity and the related metabolic diseases have led us to examine visfatin levels and its liver gene expression in morbidly obese women with non-alcoholic fatty liver disease (NAFLD). We examined the circulating levels of visfatin by ELISA in serum samples from 95 morbidly obese women (MO) (BMI&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;40 kg/m(2)) who underwent bariatric surgery and 38 normal weight control women (BMI&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;25 kg/m(2)). We analysed visfatin liver and adipose tissue mRNA expression by RT-PCR. We evaluated the circulating levels and gene expression of adiponectin, resistin, RBP4, TNFα, IL6 and CRP. Serum visfatin was significantly higher in MO compared with controls, and also in MO with NAFLD was significantly higher than MO with normal liver. We found that NAFLD diabetic patients presented similar serum visfatin levels than non-diabetic. Serum visfatin correlated with IL6 (r=0.496; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and CRP levels (r=0.241; p=0.049). Liver visfatin expression was significantly higher in MO compared to controls and was also…

Research paper thumbnail of Anti-inflammatory Profile of FTO Gene Expression in Adipose Tissues From Morbidly Obese Women

Cellular Physiology and Biochemistry, 2010

Background: The fat mass and obesity associated (FTO) gene has been found to contribute to the ri... more Background: The fat mass and obesity associated (FTO) gene has been found to contribute to the risk of obesity in humans, but the function and regulation of FTO mRNA expression in adipose tissues remain to be clarified. Our aims were to assess the FTO gene expression in subcutaneous and visceral adipose tissues from morbidly obese women and its relation with obesity, insulin resistance indices, and most importantly, to obesity-related inflammatory markers. Methods: Paired subcutaneous and visceral fat were excised from 33 morbidly obese women and 12 control women who underwent bariatric surgery by laparoscopic gastric bypass and elective surgery respectively. Adipose tissue mRNA expression was determined by real time RT-PCR. Results: FTO mRNA expression in visceral adipose tissue (VAT) was significantly higher than in subcutaneous adipose tissue (SAT) from obese but not control patients. SAT FTO expression was reduced in obese women compared to control subjects. It correlated negatively with BMI and insulin resistance indices. FTO expression in SAT was positively related to both circulating and mRNA levels of adiponectin, to adiponectin receptor and to PPAR-δ expression, but negatively with IL-6 gene expression and with circulating levels of leptin. FTO in VAT was also positively correlated with adiponectin, adiponectin receptor and PPAR-δ mRNA expression. Conclusion: FTO expression in subcutaneous adipose tissue negatively correlates with obesity and insulin resistance. On the other hand, FTO presents a positive association with the expression of adiponectin, an anti-inflammatory adipokine, and with PPAR-δ in both adipose tissues. Taken together, our results suggest that FTO is associated with an anti-inflammatory behaviour in morbid obesity.

Research paper thumbnail of Expression of Jejunal Taste Receptors in Women with Morbid Obesity

Nutrients

Nutrient sensing plays important roles in promoting satiety and maintaining good homeostatic cont... more Nutrient sensing plays important roles in promoting satiety and maintaining good homeostatic control. Taste receptors (TAS) are located through the gastrointestinal tract, and recent studies have shown they have a relationship with metabolic disorders. The aim of this study was to analyze the jejunal expression of TAS1R2, TAS1R3, TAS2R14 and TAS2R38 in women with morbid obesity, first classified according to metabolic syndrome presence (MetS; n = 24) or absence (non-MetS; n = 45) and then classified according to hepatic histology as normal liver (n = 28) or nonalcoholic fatty liver disease (n = 41). Regarding MetS, we found decreased expression of TAS2R14 in MetS patients. However, when we subclassified patients according to liver histology, we did not find differences between groups. We found negative correlations between glucose levels, triglycerides and MetS with TAS1R3 expression. Moreover, TAS2R14 jejunal expression correlated negatively with the presence of MetS and ghrelin le...

Research paper thumbnail of External match loads imposed upon Ultimate Frisbee players: A comparison between playing positions

Science & Sports, 2021

Research paper thumbnail of Laparoscopic sleeve gastrectomy alters 1H-NMR-measured lipoprotein and glycoprotein profile in patients with severe obesity and nonalcoholic fatty liver disease

Scientific Reports, 2021

Patients with morbid obesity frequently present non-alcoholic fatty liver (NAFL) and non-alcoholi... more Patients with morbid obesity frequently present non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) associated with pro-atherogenic alterations. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for weight reduction, and for the remission of hepatic alterations. Using 1H-nuclear magnetic resonance (1H-NMR), we investigated the effects of LSG on lipoprotein and glycoprotein profile in patients with morbid obesity and liver disease. We included 154 patients with morbid obesity (49 non-NASH, 54 uncertain NASH, 51 definite NASH). A blood sample was obtained before surgery and, in patients with definite NASH, one year after surgery. Patients with NASH had increased concentrations of medium and small VLDL particles, VLDL and IDL cholesterol concentrations, IDL, LDL, and HDL triglyceride concentrations, and elevated glycoprotein levels. These changes were more marked in patients with type 2 diabetes mellitus. LSG produced significant decreases in the con...

Research paper thumbnail of Relationship between IL-8 Circulating Levels and TLR2 Hepatic Expression in Women with Morbid Obesity and Nonalcoholic Steatohepatitis

International Journal of Molecular Sciences, 2020

The progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH... more The progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is linked to systemic inflammation. Currently, two of the aspects that need further investigation are diagnosis and treatment of NASH. In this sense, the aim of this study was to assess the relationship between circulating levels of cytokines, hepatic expression of toll-like receptors (TLRs), and degrees of NAFLD, and to investigate whether these levels could serve as noninvasive biomarkers of NASH. The present study assessed plasma levels of cytokines in 29 normal-weight women and 82 women with morbid obesity (MO) (subclassified: normal liver (n = 29), simple steatosis (n = 32), and NASH (n = 21)). We used enzyme-linked immunosorbent assays (ELISAs) to quantify cytokine and TLR4 levels and RTqPCR to assess TLRs hepatic expression. IL-1β, IL-8, IL-10, TNF-α, tPAI-1, and MCP-1 levels were increased, and adiponectin levels were decreased in women with MO. IL-8 was significantly higher in...

Research paper thumbnail of Influence of opponent ranking on the physical demands encountered during Ultimate Frisbee match-play

Sports Biomechanics, 2020

There is a lack of evidence regarding the match demands encountered in elite Ultimate Frisbee (UF... more There is a lack of evidence regarding the match demands encountered in elite Ultimate Frisbee (UF) overall and dependent upon opponent ranking. These data may be useful to elite UF coaches to implement optimal training loads and recovery strategies. Therefore, this study quantified the physical demands of elite UF match-play and analysed differences in demands according to opponent ranking. Twelve UF players from the same national team participated in the study. An observational design was used to compare the physical demands encountered by players between opponents carrying different rankings (1st, 3rd, 4th, and 5th) during four official matches in a 5-team competition. No significant differences (p > 0.05) in sprinting and repeated-sprinting activity were evident across UF matches between opponents. In contrast, a higher (moderate-large) quantity and greater intensities of body impacts were observed in UF matches played against higher-ranked (1st) compared to lower-ranked teams (3rd, 4th, and 5th). Additionally, greater (moderate-large) PL and metabolic power were observed in matches played against higher-ranked (1st) compared to lower-ranked teams (3rd and 4th). These findings suggest coaches may need to reduce the training loads in the next days after the matches played against higher-ranked opponents compared to when facing lower-ranked opponents.

Research paper thumbnail of Plasma metabolic alterations in patients with severe obesity and non-alcoholic steatohepatitis

Alimentary Pharmacology & Therapeutics, 2019

Background: Obesity can influence hepatic mitochondrial function, and cause nonalcoholic steatohe... more Background: Obesity can influence hepatic mitochondrial function, and cause nonalcoholic steatohepatitis (NASH). Diagnosis and follow-up rely on invasive liver biopsy so blood-based markers are urgently required. Aim: To investigate whether values of circulating metabolites from energy and onecarbon (1-C) metabolism may: (a) reflect hepatic mitochondrial flexibility failure and (b) act as NASH biomarkers. Methods: Patients with severe obesity undergoing bariatric surgery (n = 270) were investigated using quantitative targeted plasma metabolomics. Comparisons were with non-obese controls without liver disease (n = 50). Obese patients with NASH (n = 53) and without NASH (n = 130) representing extreme groups of liver disease were assessed to test the diagnostic ability of the measured circulating metabolites. Paired liver biopsy and plasma samples from NASH patients were available 1 year post-surgery and were evaluated to monitor metabolomic changes with liver damage resolution. Results: We identified correlations between human liver metabolism and obesity. High-plasma α-ketoglutarate (α-KG) and lactate concentrations in NASH patients indicating citric acid cycle replenishment via glutaminolysis might also be a crucial point in NASH onset. Plasma measurements of α-KG, β-hydroxybutyrate, pyruvate and oxaloacetate reduced the uncertainty in clinical diagnosis of NASH [area under receiver operating characteristic curve (AUC) of 0.826] and predicted NASH resolution without ambiguity (AUC of 0.999). Conclusion: Changes in plasma mitochondrial metabolites appear to be associated with NASH. These metabolic responses may be dynamically remodelled following resolution of liver damage through massive weight loss.

Research paper thumbnail of Low Circulating Levels of Neurotensin in Women with Nonalcoholic Fatty Liver Disease Associated with Severe Obesity

Obesity (Silver Spring, Md.), Feb 25, 2017

This study was performed to investigate neurotensin plasma levels in patients with nonalcoholic f... more This study was performed to investigate neurotensin plasma levels in patients with nonalcoholic fatty liver disease (NAFLD) associated with severe obesity. The plasma levels of neurotensin in 20 women with normal weight and 51 women with morbid obesity (MO) were measured, and women were subclassified according to their hepatic histology as having MO without NAFLD (n = 18) or MO with NAFLD (n = 33). The NAFLD group included 15 women with simple steatosis (SS) and 18 women with nonalcoholic steatohepatitis (NASH). To quantify neurotensin in plasma, a multiplex sandwich immunoassay with a Luminex magnetic bead-based platform was used. Neurotensin levels were significantly decreased (P = 0.001) in women with MO and NAFLD (3.62 ± 0.85 ng/mL), compared with women with MO and normal liver function (11.65 ± 1.95 ng/mL; P = 0.001) and women with normal weight (13.68 ± 2.58 ng/mL; P = 0.001). There was no difference in levels between women with SS and women with NASH (P = 0.415). Circulating ...

Research paper thumbnail of Hepcidin in morbidly obese women with non-alcoholic fatty liver disease

PloS one, 2017

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in We... more Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Both iron and lipid metabolism seem to be involved in its pathogenesis. We aimed to assess the relationship between levels of hepcidin, the master iron-regulatory protein, in plasma and the presence of NAFLD in morbidly obese (MO) patients, and to investigate the association between the hepatic expression of the main iron and lipid metabolism -related genes. Enzyme-linked immunosorbent assay was used to measure plasma hepcidin levels in 49 normal-weight control women, 23 MO women with normal liver (NL) histology and 46 MO women with NAFLD. The mRNA expression of hepcidin, the main iron metabolism-related genes, and the main lipid-metabolism genes was quantified by qRT-PCR in liver biopsies from members of the MO group undergoing bariatric surgery. Circulating hepcidin levels were significantly greater in MO than in normal-weight control women. However, there were no sign...

Research paper thumbnail of miR33a/miR33b* and miR122 as Possible Contributors to Hepatic Lipid Metabolism in Obese Women with Nonalcoholic Fatty Liver Disease

International Journal of Molecular Sciences, 2016

Specific miRNA expression profiles have been shown to be associated with nonalcoholic fatty liver... more Specific miRNA expression profiles have been shown to be associated with nonalcoholic fatty liver disease (NAFLD). We examined the correlation between the circulating levels and hepatic expression of miR122 and miR33a/b*, the key lipid metabolism-related gene expression and the clinicopathological factors of obese women with NAFLD. We measured miR122 and miR33a/b* expression in liver samples from 62 morbidly obese (MO), 30 moderately obese (ModO), and eight normal-weight controls. MiR122 and miR33a/b* expression was analyzed by qRT-PCR. Additionally, miR122 and miR33b* circulating levels were analyzed in 122 women. Hepatic miR33b* expression was increased in MO compared to ModO and controls, whereas miR122 expression was decreased in the MO group compared to ModO. In obese cohorts, miR33b* expression was increased in nonalcoholic steatohepatitis (NASH). Regarding circulating levels, MO patients with NASH showed higher miR122 levels than MO with simple steatosis (SS). These circulating levels are good predictors of histological features associated with disease severity. MO is associated with altered hepatic miRNA expression. In obese women, higher miR33b* liver expression is associated with NASH. Moreover, multiple correlations between miRNAs and the expression of genes related to lipid metabolism were found, that would suggest a miRNA-host gene circuit. Finally, miR122 circulating levels could be included in a panel of different biomarkers to improve accuracy in the non-invasive diagnosis of NASH.

Research paper thumbnail of Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

PloS one, 2016

Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from si... more Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS) and steatohepatitis (NASH) cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients. We used a gas chromatography-quadruple time-of-flight-mass spectrometry analysis to quantify alpha-ketoglutarate in serum from normal-weight subjects (n = 30) and morbidly obese women (n = 97) with or without NAFLD. We found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, ...

Research paper thumbnail of Downregulation of de Novo Fatty Acid Synthesis in Subcutaneous Adipose Tissue of Moderately Obese Women

International Journal of Molecular Sciences, 2015

The purpose of this work was to evaluate the expression of fatty acid metabolism-related genes in... more The purpose of this work was to evaluate the expression of fatty acid metabolism-related genes in human adipose tissue from moderately obese women. We used qRT-PCR and Western Blot to analyze visceral (VAT) and subcutaneous (SAT) adipose tissue mRNA expression involved in de novo fatty acid synthesis (ACC1, FAS), fatty acid oxidation (PPARα, PPARδ) and inflammation (IL6, TNFα), in normal weight control women (BMI < 25 kg/m 2 , n = 35) and moderately obese women (BMI 30-38 kg/m 2 , n = 55). In SAT, ACC1, FAS and PPARα mRNA expression were significantly decreased in moderately obese women compared to controls. The downregulation reported in SAT was more pronounced when BMI increased. In VAT, lipogenic-related genes and PPARα were similar in both groups. Only PPARδ gene expression was significantly increased in moderately obese women. As far as inflammation is concerned, TNFα and IL6 were significantly increased in moderate obesity in both tissues. Our results indicate that there is a progressive downregulation in lipogenesis in SAT as BMI increases, which suggests that SAT decreases the synthesis of fatty acid de novo during the development of obesity, whereas in VAT lipogenesis remains active regardless of the degree of obesity.

Research paper thumbnail of Cirugía experimental y obesidad mórbida

Research paper thumbnail of Tissue-specific DNA methylation profiles regulate liver-specific expression of the APOA1/C3/A4/A5 cluster and can be manipulated with demethylating agents on intestinal cells

Atherosclerosis, 2014

Objective: The tissue-specific expression profiles of genes within the APOA1/C3/A4/A5 cluster pla... more Objective: The tissue-specific expression profiles of genes within the APOA1/C3/A4/A5 cluster play an important role in lipid metabolism regulation. We hypothesize that the tissue-specific expression of the APOA1/C3/A4/A5 gene cluster will show an inverse pattern with DNA methylation, and that repression in non-or low-expressing tissue, such as the intestine, can be reversed using epigenetic drugs. Methods and results: We analyzed DNA samples from different human adult tissues (liver, intestine, leukocytes, brain, kidney, pancreas, muscle and sperm) using the Infinium HumanMethyation450 BeadChip array. DNA methylation profiles in APOA1/C3/A4/A5 gene cluster were confirmed by bisulfite PCR and pyrosequencing. To determine whether the observed tissue-specific methylation was associated with the expression profile we exposed intestinal TC7/Caco-2 cells to the demethylating agent 5-Aza-2 0-deoxycytidine and monitored intestinal APOA1/C3/A4/A5 transcript re-expression by RT-qPCR. The promoters of APOA1, APOC3 and APOA5 genes were less methylated in liver compared to other tissues, and APOA4 gene was highly methylated in most tissues and partially methylated in liver and intestine. In TC7/Caco-2 cells, 5-Aza-2 0-deoxycytidine treatment induced a decrease between 37 and 24% in the methylation levels of APOA1/C3/A4/A5 genes and a concomitant re-expression mainly in APOA1, APOA4 and APOA5 genes ranging from 22 to 600%. Conclusions: We have determined the methylation patterns of the APOA1/C3/ A4/A5 cluster that may be directly involved in the transcriptional regulation of this cluster. DNA demethylation of intestinal cells increases the RNA levels especially of APOA1, APOA4 and APOA5 genes.

Research paper thumbnail of Endocannabinoid Receptors Gene Expression in Morbidly Obese Women with Nonalcoholic Fatty Liver Disease

BioMed Research International, 2014

Background. Recent reports suggest a role for the endocannabinoid system in the pathology of nona... more Background. Recent reports suggest a role for the endocannabinoid system in the pathology of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between liver expression of cannabinoid (CB) receptor subtypes, CB1 and CB2, in morbidly obese (MO) women with different histological stages of NAFLD.Methods. We analysed hepatic CB1 and CB2 mRNA expression, and the expression of genes involved in lipid metabolism in 72 MO women, subclassified by liver histology into MO with normal liver (NL,n=16), simple steatosis (SS,n=28), and nonalcoholic steatohepatitis (NASH,n=28) by enzyme-linked immunosorbent assay and RT-PCR.Results. We found that CB1 mRNA expression was significantly higher in NASH compared with SS and correlated negatively with PPARα. Regarding CB2, CB2 mRNA expression correlated positively with ACC1, PPARγ, IL6, TNFα, resistin, and adiponectin.Conclusions. The increased expression of CB1 in NASH and the negative correlation with PP...

Research paper thumbnail of Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

International Journal of Molecular Sciences, 2014

Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the... more Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in

Research paper thumbnail of Retinol binding protein-4 circulating levels were higher in nonalcoholic fatty liver disease vs. histologically normal liver from morbidly obese women

Obesity, 2013

nature publishing group articles Genetics IntroductIon Nonalcoholic fatty liver disease (NAFLD) h... more nature publishing group articles Genetics IntroductIon Nonalcoholic fatty liver disease (NAFLD) has frequently been associated with obesity, type 2 diabetes mellitus (T2DM), hyperlipidemia, and insulin resistance, which are the main features of metabolic syndrome (1,2). NAFLD is an increasingly recognized condition that has become the most common liver disorder in the developed world (1). NAFLD causes a wide spectrum of liver damage, ranging from simple steatosis (SS) to cirrhosis. In most cases, SS does not progress to a more severe disease, but ~20-30% of patients have histological signs of fibrosis and necroinflammation, indicating a presence of nonalcoholic steatohepatitis (NASH) (3). The pathogenesis of NAFLD is poorly understood and much of the current opinion remains hypothetical. Obesity is considered an important risk factor, though not all patients with NAFLD are obese (4). In obesity, an altered secretion of proteins takes place in the adipose tissue, the so-called adipokines, which have wide-ranging endocrine and paracrine effects on general metabolism (5). These adipokines are considered important determinants of obesity-related disorders such as insulin resistance, inflammation, and dyslipidemia (6). Consequently, there is growing evidence that adipokines are one of the causal links between obesity and NAFLD (7). A recently identified adipokine is the retinol binding protein-4 (RBP4), the specific carrier protein of retinol (vitamin A) in the blood. Although the major tissue site of RBP4 synthesis in the body is the liver, other sites of synthesis have been reported such as adipose tissues, kidney, and brain (8-10). It has been put forward that adipose tissue in humans, as occurs in mice, has the second highest level of RBP4 expression (8). Circulating RBP4 levels have been associated with estimations of adiposity and insulin resistance (11-13). Interestingly, we and others have reported a downregulation of RBP4 messenger RNA (mRNA) in subcutaneous adipose tissue (SAT)

Research paper thumbnail of Clinical and adipocytokine changes after bariatric surgery in morbidly obese women

Obesity, 2013

Objective: Recent studies report the effect of bariatric surgery on glycaemia control and prevent... more Objective: Recent studies report the effect of bariatric surgery on glycaemia control and prevention of type-2-diabetes in obese patients. This study is about the pathophysiological mechanisms associated to these changes. Design and Methods: Circulating levels of receptors of tumor necrosis factor (TNF-RI, TNF-RII), visfatin, high molecular weight (HMW) adiponectin, and C reactive protein (CRP) in 30 morbidly obese women (body mass index, BMI>40 kg/m 2) and 60 normal-weight controls (BMI>25 kg/m 2) were analyzed. Morbidly obese were studied at three time-points: before surgery (baseline), and 6 and 12 months after. Results: After surgery, the levels of TNF-RI, TNF-RII, visfatin, and CRP were significantly lower than its baseline levels, whereas HMW adiponectin was higher. Fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA2-IR) levels were markedly lower postoperatively. High density lipoproteins (HDL) moderately increased, and triglyceride levels had sharply decreased. The study of the predictive value of variables indicated that preoperative levels of TNF-RI and visfatin correlated positively with levels of glucose, insulin, glycosylated hemoglobin A1c, and HOMA2-IR postoperatively, whereas adiponectin levels correlated negatively. Baseline CRP levels negatively linked to HDL and TNF-RII positively to triglyceride. Conclusions: The preoperative profile with high levels of proinflammatory adipocytokines is linked to smaller improvements in glucose homeostasis and lipid factors. The use of a range of biomarkers may predict the level of metabolic changes following bariatric surgery.

Research paper thumbnail of Inhibition of hepatic cell nuclear DNA fragmentation by zinc in carbon tetrachloride-treated rats

Journal of Hepatology, 1999

Background/Aims: The aims of this study were to ascertain: 1) whether hepatic cell DNA fragmentat... more Background/Aims: The aims of this study were to ascertain: 1) whether hepatic cell DNA fragmentation is increased in rats with early stages of liver disease induced by carbon tetrachloride; 2) whether the inhibition of DNA cleavage is involved in the hepatoprotective effects of zinc; and 3) if relationships exist between DNA fragmentation and the onset of fibrosis in this experimental model. Methods: Twenty-one treated rats and 23 controls were divided into two groups to receive either a standard diet or one supplemented with zinc. All the animals were sacrificed 1 week later for histological and biochemical assessments, which included a DNA fragmentation index, hepatic zinc and metallothionein concentrations, fibrosis measured by hepatic hydroxyproline concentration and plasma alanine aminotransferase activity. Results: Hepatic cell DNA fragmentation was in-T   an increasing body of evidence, from human and experimental studies, suggesting that zinc could be a beneficial agent in the protection against hepatotoxicity (1,2). A close association was found between low serum zinc content and fibrogenesis in patients with alcoholic liver disease (3). Additionally, studies in a model of cirrhosis, experimentally induced in the rat by chronic carbon tetrachloride administration, indicated that zinc supplementation decreased hepatic collagen content and fibrogenesis, activated collagenolytic enzymes and limited the pro

Research paper thumbnail of Plasma visfatin levels and gene expression in morbidly obese women with associated fatty liver disease

Clinical Biochemistry, 2013

The few studies on the physiopathological role of visfatin in morbid obesity and the related meta... more The few studies on the physiopathological role of visfatin in morbid obesity and the related metabolic diseases have led us to examine visfatin levels and its liver gene expression in morbidly obese women with non-alcoholic fatty liver disease (NAFLD). We examined the circulating levels of visfatin by ELISA in serum samples from 95 morbidly obese women (MO) (BMI&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;40 kg/m(2)) who underwent bariatric surgery and 38 normal weight control women (BMI&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;25 kg/m(2)). We analysed visfatin liver and adipose tissue mRNA expression by RT-PCR. We evaluated the circulating levels and gene expression of adiponectin, resistin, RBP4, TNFα, IL6 and CRP. Serum visfatin was significantly higher in MO compared with controls, and also in MO with NAFLD was significantly higher than MO with normal liver. We found that NAFLD diabetic patients presented similar serum visfatin levels than non-diabetic. Serum visfatin correlated with IL6 (r=0.496; p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and CRP levels (r=0.241; p=0.049). Liver visfatin expression was significantly higher in MO compared to controls and was also…

Research paper thumbnail of Anti-inflammatory Profile of FTO Gene Expression in Adipose Tissues From Morbidly Obese Women

Cellular Physiology and Biochemistry, 2010

Background: The fat mass and obesity associated (FTO) gene has been found to contribute to the ri... more Background: The fat mass and obesity associated (FTO) gene has been found to contribute to the risk of obesity in humans, but the function and regulation of FTO mRNA expression in adipose tissues remain to be clarified. Our aims were to assess the FTO gene expression in subcutaneous and visceral adipose tissues from morbidly obese women and its relation with obesity, insulin resistance indices, and most importantly, to obesity-related inflammatory markers. Methods: Paired subcutaneous and visceral fat were excised from 33 morbidly obese women and 12 control women who underwent bariatric surgery by laparoscopic gastric bypass and elective surgery respectively. Adipose tissue mRNA expression was determined by real time RT-PCR. Results: FTO mRNA expression in visceral adipose tissue (VAT) was significantly higher than in subcutaneous adipose tissue (SAT) from obese but not control patients. SAT FTO expression was reduced in obese women compared to control subjects. It correlated negatively with BMI and insulin resistance indices. FTO expression in SAT was positively related to both circulating and mRNA levels of adiponectin, to adiponectin receptor and to PPAR-δ expression, but negatively with IL-6 gene expression and with circulating levels of leptin. FTO in VAT was also positively correlated with adiponectin, adiponectin receptor and PPAR-δ mRNA expression. Conclusion: FTO expression in subcutaneous adipose tissue negatively correlates with obesity and insulin resistance. On the other hand, FTO presents a positive association with the expression of adiponectin, an anti-inflammatory adipokine, and with PPAR-δ in both adipose tissues. Taken together, our results suggest that FTO is associated with an anti-inflammatory behaviour in morbid obesity.