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Teresa Auguet,
Ximena Terra,
Mercè Hernández,
Fàtima Sabench,
Jose Antonio Porras,
Josep Maria Orellana-Gavaldà,
Jordi Llutart,
Esther Guiu-Jurado,
Alba Berlanga,
Salomé Martinez,
Carmen Aguilar, Daniel Del Castillo,
Cristóbal Richart
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ABSTRACT: Objective: Recent studies report the effect of bariatric surgery on glycaemia control and prevention of type-2-diabetes in obese patients. This is a study into the pathophysiological mechanisms associated to these changes. Design and Methods: We analysed circulating levels of TNF-RI, TNF-RII, visfatin, HMW adiponectin and CRP in 30 morbidly obese women (BMI>40 kg/m(2) ) and 60 normal-weight controls (BMI>25 kg/m(2) ). 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 HOMA2-IR levels were markedly lower postoperatively. HDL levels 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, HbA1c 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.
Obesity 03/2013; · 4.28 Impact Factor
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Ximena Terra,
Teresa Auguet,
Montserrat Broch,
Fàtima Sabench,
Mercè Hernández,
Rosa M Pastor,
Isabel M Quesada,
Anna Luna,
Carmen Aguilar, Daniel Del Castillo,
Cristóbal Richart
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ABSTRACT: 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.
We performed a cross-sectional analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and liver samples from four lean and 45 MO women with or without NAFLD by enzyme-linked immunosorbent assay and real-time reverse transcription-PCR. We also studied RBP4 expression in HepG2 hepatocytes under various inflammatory stimuli.
Circulating RBP4 levels were higher in MO women, and specifically, in MO subjects with NAFLD compared with normal liver controls (lean and MO). RBP4 liver expression was higher in nonalcoholic steatohepatitis (NASH)-moderate/severe than in NASHmild. Overall RBP4 gene expression was higher in liver than in adipose tissues. Among them, the higher expression corresponded to SAT. VAT expression was lower in the MO cohort. In HepG2, RBP4 mRNA expression was reduced by tumor necrosis factor (TNF)-α and increased by adiponectin treatment.
The results obtained in MO women with NAFLD, brings up the use of RBP4 and other adipokines as a panel of noninvasive molecular biomarkers when NAFLD is suspected. Further studies are needed with other obesity groups.
Obesity 01/2013; 21(1):170-7. · 4.28 Impact Factor
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Teresa Auguet,
Ximena Terra,
Jose Antonio Porras,
Josep Maria Orellana-Gavaldà,
Salomé Martinez,
Carmen Aguilar,
Anna Lucas,
Silvia Pellitero,
Mercé Hernández, Daniel Del Castillo,
Cristóbal Richart
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ABSTRACT: OBJECTIVES: 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). DESIGN AND METHODS: We examined the circulating levels of visfatin by ELISA in serum samples from 95 morbidly obese women (MO) (BMI>40kg/m(2)) who underwent bariatric surgery and 38 normal weight control women (BMI<25kg/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. RESULTS: 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<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 significantly higher in MO with NAFLD than in MO with normal liver. Visfatin liver expression correlated positively with resistin (r=0.436, p=0.018) and TNFα expression (r=0.328, p=0.028). Visfatin expression in adipose tissues was similar among the MO groups analysed. CONCLUSION: Serum visfatin and its liver expression are higher in MO women with NAFLD, irrespective of the presence of diabetes. Serum visfatin and its liver expression correlate positively with pro-inflammatory factors. These findings suggest that visfatin may be a molecule related with fat inflammation in morbid obesity and fatty liver disease.
Clinical biochemistry 11/2012; · 2.02 Impact Factor
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Ximena Terra,
Teresa Auguet,
Isabel Quesada,
Carmen Aguilar,
Anna Maria Luna,
Mercé Hernández,
Fátima Sabench,
José Antonio Porras,
Salomé Martínez,
Anna Lucas,
Silvia Pellitero,
Jordi Llutart, Daniel Del Castillo,
Cristóbal Richart
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ABSTRACT: 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. Design, patients and measurements We analysed circulating levels of several adipo/cytokines in 133 Spanish women: 40 lean (C) [body mass index (BMI) < 25 kg/m(2) ] and 93 morbidly obese (MO) (BMI > 40 kg/m(2) ). In the MO group, we found 31 diabetic and 62 nondiabetic subjects. We obtained follow-up blood samples at 6 and 12 months after bariatric surgery from 30 MO patients. We determined the circulating levels of visfatin, adiponectin, interleukin-6 (IL6), C-reactive protein (CRP), resistin and tumour necrosis factor-α (TNFα) by ELISA, and visfatin, adiponectin, IL6, resistin and TNFα gene expression in SAT and VAT by real-time RT-PCR. Results Circulating visfatin levels were higher in MO women compared with lean controls (C = 1·43 ± 0·14 μg/l, MO = 3·60 ± 0·29 μg/l, P < 0·001). After bariatric surgery-induced weight loss, visfatin levels were reduced significantly over 12 months. Visfatin expression in SAT and VAT was similar, but significantly higher in MO compared to C and independent of the presence of diabetes mellitus. Circulating visfatin levels were positively related to IL6 and CRP levels. Visfatin gene expression in VAT and SAT was strongly related to IL6 and TNFα expression. Conclusion In a homogeneous cohort of morbidly obese women, our findings show that visfatin has a strong relationship with pro-inflammatory factors in severe obesity.
Clinical Endocrinology 12/2011; 77(5):691-8. · 3.17 Impact Factor
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ABSTRACT: Because the role of lipocalin 2 (LCN2) in morbid obesity is still not well defined, the aim of this study was to evaluate the circulating levels and the expression of LCN2 in visceral (VAT) and subcutaneous adipose tissue (SAT) in severely obese (SO) women. We also analyzed its relationship with inflammatory cytokines in the same subjects. The study comprised 90 white women, 39 of whom were lean controls (BMI ≤25 kg/m(2)) and 51 SO (BMI ≥40 kg/m(2)). Both circulating and adipose tissue levels of LCN2 were quantified by enzyme-linked immunosorbent assays. LCN2 mRNA levels from VAT and SAT were assessed by real-time reverse transcriptase-PCR (n = 60). LCN2 serum levels were significantly higher in the SO women than in the lean controls (P = 0.042), and were found to be strongly correlated with tumor necrosis factor receptor I (TNFR1) circulating levels. In the SO cohort, LCN2 serum levels were also associated with higher BMI values, but not with the homeostasis model assessments of insulin resistance (HOMA2-IR). LCN2 mRNA expression was markedly higher in SO women than in lean women in both VAT (P = 0.043) and SAT (P = 0.031). In SAT, LCN2 was negatively correlated with adiponectin and adiponectin receptor-2 expression, and positively with interleukin-6 (IL-6) expression. A strong positive correlation was also found between LCN2 expression and the mean diameter of adipocytes in VAT. Our results revealed that the circulating level of LCN2 is associated with obesity and BMI. LCN2 mRNA is over-expressed in adipose tissue from SO subjects. Finally, the expression of LCN2 is strongly related to an expression profile of proinflammatory cytokines but not to insulin resistance in nondiabetic SO women.
Obesity 03/2011; 19(12):2295-300. · 4.28 Impact Factor
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Teresa Auguet,
Yunuen Quintero,
David Riesco,
Beatriz Morancho,
Ximena Terra,
Anna Crescenti,
Montserrat Broch,
Carmen Aguilar,
Montserrat Olona,
José Antonio Porras,
Mercè Hernandez,
Fátima Sabench, Daniel del Castillo,
Cristóbal Richart
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ABSTRACT: Vaspin 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.
We 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.
Serum 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.
The 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.
BMC Medical Genetics 01/2011; 12:60. · 2.33 Impact Factor
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ABSTRACT: 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.
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.
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.
Our results indicate that serum FABP4 is associated with inflammatory factors related to obesity and MS in non-diabetic morbidly obese women.
European Journal of Endocrinology 01/2011; 164(4):539-47. · 3.42 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
Cellular Physiology and Biochemistry 01/2010; 26(6):1041-50. · 2.86 Impact Factor