Metabolism of the brown adipose tissue in animal models of insulin resistance: Goto-Kakizaki and obese Wistar rats

Abstract

Overweight and obesity are related to several disorders, such as insulin resistance, chronic inflammation, Type 2 Diabetes Mellitus, cardiovascular diseases, dyslipidemia, metabolic syndrome, and cancer. Brown Adipose Tissue (BAT) has been proposed as a potential intervention for obesity because its high metabolic capacity to dissipate energy as heat without ATP synthesis, enhancing energy expenditure. In addition, BAT is responsive to the insulin and it helps to improve glycemic homeostasis, but the precise mechanisms are not completely understood yet. The aims of this project are to characterize the role of BAT in three animal models of insulin resistance: obese (Wistar rats submitted to a high-fat diet or high-fat plus high-sugar diet) and non-obese (Goto-Kakizaki rats, genetically predisposed to develop IR) animals. We will investigate the following parameters: 1) BAT metabolism in isolated mitochondria; 2) secretion of molecules by BAT (batokines), and 3) expression of proteins involved in the insulin-signaling pathway (IRS-1, Akt, GSK-3, PKC-q, e PI3-K). Therefore, this project will be important to characterize the BAT adipose tissue function and its metabolic influence in the insulin resistant state in different animal models (obese and non- obese rats). Elucidation of the BAT participation in these models is primordial, since it can help to direct new studies and strategies for improving glycemic homeostasis. (AU)