Brown adipose tissue responds to cold and adrenergic stimulation by induction of FGF21

Fibroblast growth factor-21 (FGF21) is a pleiotropic protein involved in glucose, lipid metabolism and energy homeostasis, with main tissues of expression being the liver and adipose tissue. Brown adipose tissue (BAT) is responsible for cold-induced thermogenesis in rodents. The role of FGF21 in BAT biology has not been investigated. In the present study, wild-type C57BL/6J mice as well as a brown adipocyte cell line were used to explore the potential role of cold exposure and β3-adrenergic stimulation in the expression of FGF21 in BAT. Our results demonstrate that short-term exposure to cold, as well as β3-adrenergic stimulation, causes a significant induction of FGF21 mRNA levels in BAT, without a concomitant increase in FGF21 plasma levels. This finding opens new routes for the potential use of pharmaceuticals that could induce FGF21 and, hence, activate BAT thermogenesis.     

Statins and transcriptional regulation: the FXR connection

Farnesoid X receptor (FXR) is a nuclear receptor involved in lipoprotein as well as glucose metabolism. Statins are widely used hypolipidemic agents with many pleiotropic actions. It is known that statins affect other nuclear hormone receptors, but no reports are available on the effect of these drugs on FXR. Employing an animal model (Syrian hamsters), we hereby present evidence to demonstrate that Simvastatin, a broadly prescribed statin, decreases the expression of FXR at both the RNA and protein levels and down-regulates its DNA-binding activity. This novel property may have important implications on the mode statins influence on lipoprotein and carbohydrate homeostasis in the organism.     

Activated hypothalamic pituitary adrenal axis in patients with metabolic syndrome

Metabolic syndrome (MetS) is correlated with the activity of hypothalamic-pituitary-adrenal axis (HPA), but the underlying mechanism still remains elusive. The aim of this study was to investigate the HPA axis function in patients with MetS. This case-control study included 159 people. They were divided into 2 groups. The first group included 73 healthy volunteers (control group: 19 males, 54 females, mean±SD: 49.9±7.5 years old, with BMI: 27.9±4.42?kg/m2) and the second group included 86 patients with MetS (case group: 48 males, 38 females, mean±SD: 52.2±7.6 years old, with BMI: 30.5±5.35?kg/m2). An oral glucose tolerance test (OGTT) was performed for all subjects after a 12-h overnight fast, and blood samples were obtained for determination of ACTH, cortisol, insulin, C-peptide, and glucose levels. Serum cortisol after an overnight dexamethasone suppression test was determined in both groups. Patients with MetS had serum cortisol levels after an overnight dexamethasone suppression test significantly higher than controls. During OGTT plasma ACTH levels were higher at all time points in patients with MetS compared to controls, whereas serum cortisol levels were comparable between the 2 groups. Plasma ACTH during OGTT was also correlated with most of the components of MetS. The HPA axis in patients with MetS seems to be more active as evidenced by the higher cortisol levels after the overnight dexamethasone suppression test and by the higher ACTH levels during OGTT. This functional hypercortisolism might be involved in the pathogenesis of the metabolic syndrome.     

Differential expression of microRNAs in adipose tissue after long-term high-fat diet-induced obesity in mice

Obesity is a major health concern worldwide which is associated with increased risk of chronic diseases such as metabolic syndrome, cardiovascular disease and cancer. The elucidation of the molecular mechanisms involved in adipogenesis and obesogenesis is of essential importance as it could lead to the identification of novel biomarkers and therapeutic targets for the development of anti-obesity drugs. MicroRNAs (miRNAs) have been shown to play regulatory roles in several biological processes. They have become a growing research field and consist of promising pharmaceutical targets in various fields such as cancer, metabolism, etc. The present study investigated the possible implication of miRNAs in adipose tissue during the development of obesity using as a model the C57BLJ6 mice fed a high-fat diet.C57BLJ6 wild type male mice were fed either a standard (SD) or a high-fat diet (HFD) for 5 months. Total RNA was prepared from white adipose tissue and was used for microRNA profiling and qPCR.Twenty-two of the most differentially expressed miRNAs, as identified by the microRNA profiling were validated using qPCR. The results of the present study confirmed previous results. The up-regulation of mmu-miR-222 and the down-regulation of mmu-miR-200b, mmu-miR-200c, mmu-miR-204, mmu-miR-30a*, mmu-miR-193, mmu-miR-378 and mmu-miR-30e* after HFD feeding has also been previously reported. On the other hand, we show for the first time the up-regulation of mmu-miR-342-3p, mmu-miR-142-3p, mmu-miR-142-5p, mmu-miR-21, mmu-miR-146a, mmu-miR-146b, mmu-miR-379 and the down-regulation of mmu-miR-122, mmu-miR-133b, mmu-miR-1, mmu-miR-30a*, mmu-miR-192 and mmu-miR-203 during the development of obesity. However, future studies are warranted in order to understand the exact role that miRNAs play in adipogenesis and obesity.