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

BACKGROUND: 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. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Upregulation of lipocalin 2 in adipose tissues of severely obese women: positive relationship with proinflammatory cytokines.

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.

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.

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.