Signaling pathways affected by fish oil in Adipose tissue-Derived Stem Cells (AdSCs) and adipocytes: correlation with metabolic, endocrine and adipogenic changes that impact its anti-Hypertrophic Obesity properties

Abstract

The present study proposes an analysis of lipid profile and functional genomics with emphasis on signaling pathways in cells from White Adipose Tissue (WAT), adipocytes and WAT-derived mesenchymal stem cells (AdSCs), using a therapeutic approach with fish oil [FO, rich in É-3 polyunsaturated Fatty Acids (FA)] in High Fat Diet (HFD)-Induced Obese (DIO) mice. The objective is to understand the mechanisms triggered by these FAs that define their anti-hypertrophic obesity properties described by our group. We hypothesized that FO modulates a "healthy" expansion of WAT during induction of obesity by HFD and therefore may act as important agent to prevent and/or treat obesity and related diseases. This hypothesis is based on: a) literature data indicating that É-3 FAs are PPAR agonists able to regulating body weight and adiposity, adipogenesis and continuous remodeling of body weight regardless of food intake; and that, improve the plasma lipid profile, glucose tolerance and inflammatory condition of obese and diabetic patients; b) previous studies of our group, demonstrating for the first time in the literature that the beneficial effects of FO on mice such as reduced fat mass, hepatic steatosis, dyslipidemia and improved insulin sensitivity is largely due to its differential effects on isolated adipocytes, reducing its hypertrophy, modulating its main metabolic activities (lipolysis and lipogenesis) and decreasing the secretion of inflammatory cytokines by these cells; c) the demonstration of browning in subcutaneous adipose deposits (under certain stimuli) and that browning inducers (from AdSCs) could soften the obesity and related diseases; d) the discovery that recruitment of new adipocytes (from ADSCs) by adipogenesis induction results in a healthy expansion of WAT and inhibits the hypertrophic obesity (or pathological WAT expansion); e) our most recent (unpublished) data demonstrating positive effects of É-3 FA on browning and adipogenesis induction. Using non-target (lipidomic) and functional genomics (PCR-array, bioinformatics and western blot tools) in ADSCs and adipocytes, we aim to elucidate some of the mechanisms of action by which the beneficial effects of FO previously observed by the group occur. (AU)