Fàtima Sabench

New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women

BackgroundVaspin and omentin are recently described molecules that belong to the adipokine family and seem to be related to metabolic risk factors. The objectives of this study were twofold: to evaluate vaspin and omentin circulating levels and mRNA expression in subcutaneous and visceral adipose tissues in non-diabetic morbidly obese women; and to assess the relationship of vaspin and omentin with anthropometric and metabolic parameters, and other adipo/cytokines.DesignWe analysed vaspin and omentin circulating levels in 71 women of European descent (40 morbidly obese [BMI ≥ 40 kg/m2] and 31 lean [BMI ≤ 25]). We assessed vaspin and omentin gene expression in paired samples of visceral and subcutaneous abdominal adipose tissue from 46 women: 40 morbidly obese and 6 lean. We determined serum vaspin and plasma omentin levels with an Enzyme-Linked Immunosorbent Assay and adipose tissue mRNA expression by real time RT-PCR.ResultsSerum vaspin levels in the morbidly obese were not significantly different from those in controls. They correlated inversely with levels of lipocalin 2 and interleukin 6. Vaspin mRNA expression was significantly higher in the morbidly obese, in both subcutaneous and visceral adipose tissue.Plasma omentin levels were significantly lower in the morbidly obese and they correlated inversely with glucidic metabolism parameters. Omentin circulating levels, then, correlated inversely with the metabolic syndrome (MS). Omentin expression in visceral adipose tissue was significantly lower in morbidly obese women than in controls.ConclusionsThe present study indicates that vaspin may have a compensatory role in the underlying inflammation of obesity. Decreased omentin circulating levels have a close association with MS in morbidly obese women.

FABP 4 is associated with inflammatory markers and metabolic syndrome in morbidly obese women.

OBJECTIVE The adipocyte/macrophage fatty acid-binding protein 4 (FABP4) has been described as a biomarker for adiposity and metabolic syndrome (MS). The aims of this study were to assess the relationship between FABP4 and inflammatory cytokines related to obesity, and to evaluate FABP4 mRNA expression in visceral and subcutaneous adipose tissue in non-diabetic morbidly obese women versus healthy lean women. METHODS We analyzed circulating levels of FABP4 in 81 Spanish women: 38 lean (body mass index (BMI)<25 kg/m(2)) and 43 morbidly obese (BMI>40 kg/m(2)). We took 30 follow-up blood samples at 6 and 12 months after bariatric surgery. We assessed FABP4 gene expression in samples of subcutaneous abdominal and visceral adipose tissue. Adipose tissue mRNA expression was determined by real-time RT-PCR. RESULTS In morbidly obese women, plasma FABP4 levels were significantly higher than in non-obese patients. These levels positively correlated with BMI, homeostasis model assessment of insulin resistance (HOMA2-IR), and plasma glucose and insulin levels. Post-operative FABP4 levels decreased by a maximum of 30% after 12 months. We also found an inverse association between FABP4 and adiponectin levels, and positive correlations between FABP4 and circulating leptin, tumor necrosis factor (TNF) receptors, C-reactive protein (CRP) and interleukin 6 levels. Linear regression analysis revealed that FABP4 was more closely related to HOMA2-IR than adiponectin, CRP, TNF-RI, or leptin. Furthermore, high circulating FABP4 levels were associated with the presence of MS. FABP4 mRNA expression in visceral adipose tissue was related to its circulating levels in morbidly obese women. CONCLUSIONS Our results indicate that serum FABP4 is associated with inflammatory factors related to obesity and MS in non-diabetic morbidly obese women.

Plasma vitamin D and parathormone are associated with obesity and atherogenic dyslipidemia: a cross-sectional study

BackgroundLow concentrations of plasma vitamin D (25(OH)D) have been associated with the development of metabolic syndrome (MetS), obesity, diabetes and cardiovascular disease. The objective of this study was to quantify the associations between 25(OH)D and parathormone (PTH) plasma levels and obesity, the presence of MetS, diabetes or atherogenic dyslipidemia (AD) in a large sample of individuals with different degrees of adiposity.MethodsRetrospective study of all patients who had attended the obesity clinics in a Spanish hospital between 2009 and 2011, and whose concentrations of PTH, 25(OH)D, calcium and alkaline phosphatase had been determined (n=316, 75.9% women). Individuals were categorized by degree of adiposity, presence of MetS, and other comorbidities.ResultsPTH increased but 25(OH)D and calcium decreased with increasing adiposity. The prevalence of 25(OH)D deficiency or insufficiency increased with obesity (<10% when BMI<45kg/m2, and 26% when >50). The prevalence of hyperparathyroidism increased from 12% in non-obese to 47.5% in morbidly obese individuals with BMI>50 kg/m2. Low plasma 25(OH)D and high PTH concentrations were associated with an increased risk of MetS and AD. These associations disappeared, except in the case of AD for 25(OH)D when adjusting for BMI. Regression analysis revealed that BMI and age or seasonality were independent predictors of PTH and 25(OH)D levels, respectively.ConclusionsBMI was the variable most strongly associated with plasma 25(OH)D and PTH concentrations in our study. Low 25(OH)D and high PTH concentrations were not independently associated with an increased risk of MetS, or diabetes. Our data support a possible contribution of plasma 25(OH)D to the pathogenesis of hypertriglyceridemia and AD through inflammation.

Immunohistochemical analysis of paraoxonases‐1 and 3 in human atheromatous plaques

Eur J Clin Invest 2011; 41 (3): 308–314

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

We aimed to analyze the retinol binding protein‐4 (RBP4) messenger RNA (mRNA) expression profiles in adipose tissues and liver of morbidly obese (MO) women with or without nonalcoholic fatty liver disease (NAFLD), and to study the relationships with other pro‐ and anti‐inflammatory adipokines in vivo and in vitro.

Mapping of the circulating metabolome reveals α-ketoglutarate as a predictor of morbid obesity-associated non-alcoholic fatty liver disease.

Background:Obesity severely affects human health, and the accompanying non-alcoholic fatty liver disease (NAFLD) is associated with high morbidity and mortality. Rapid and non-invasive methods to detect this condition may substantially improve clinical care.Methods:We used liquid and gas chromatography–quadruple time-of-flight–mass spectrometry (LC/GC-QTOF-MS) analysis in a non-targeted metabolomics approach on the plasma from morbidly obese patients undergoing bariatric surgery to gain a comprehensive measure of metabolite levels. On the basis of these findings, we developed a method (GC-QTOF-MS) for the accurate quantification of plasma α-ketoglutarate to explore its potential as a novel biomarker for the detection of NAFLD.Results:Plasma biochemical differences were observed between patients with and without NAFLD indicating that the accumulation of lipids in hepatocytes decreased β-oxidation energy production, reduced liver function and altered glucose metabolism. The results obtained from the plasma analysis suggest pathophysiological insights that link lipid and glucose disturbances with α-ketoglutarate. Plasma α-ketoglutarate levels are significantly increased in obese patients compared with lean controls. Among obese patients, the measurement of this metabolite differentiates between those with or without NAFLD. Data from the liver were consistent with data from plasma. Clinical utility was assessed, and the results revealed that plasma α-ketoglutarate is a fair-to-good biomarker in patients (n=230). Other common laboratory liver tests used in routine application did not favourably compare.Conclusion:Plasma α-ketoglutarate is superior to common liver function tests in obese patients as a surrogate biomarker of NAFLD. The measurement of this biomarker may potentiate the search for a therapeutic approach, may decrease the need for liver biopsy and may be useful in the assessment of disease progression.

Increased levels and adipose tissue expression of visfatin in morbidly obese women: the relationship with pro‐inflammatory cytokines

Objective  The controversial results on the physiopathological role of visfatin led us to examine both circulating visfatin levels and gene expression in visceral (VAT) and subcutaneous fat (SAT) in a homogeneous group of morbidly obese women.

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

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 morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis.

Anti-inflammatory profile of FTO gene expression in adipose tissues from morbidly obese women.

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 by-pass 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-Δexpression, 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.

Clinical and adipocytokine changes after bariatric surgery in morbidly obese women

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.