Role of brown adipose tissue in modulating adipose tissue inflammation and insulin resistance in high-fat diet fed mice

Abstract

Obesity results in the chronic activation of innate immune system and subsequently sets in diabetes. Aim of the study was to investigate the immunometabolic role of brown adipose tissue (BAT) in the obesity. We performed both BAT transplantation as well as extirpation experiments in the mouse model of high-fat diet (HFD)-induced obesity. We carried out immune cell profiling in the stromal vascular fraction (SVF) isolated from epididymal white adipose tissue (eWAT). BAT transplantation reversed HFD-induced increase in body weight gain and insulin resistance without altering diet intake. Importantly, BAT transplantation attenuated the obesity-associated adipose tissue inflammation in terms of decreased pro-inflammatory M1-macrophages, cytotoxic CD8a T-cells and restored anti-inflammatory regulatory T-cells (Tregs) in the eWAT. BAT transplantation also improved endogenous BAT activity by elevating protein expression of browning markers (UCP-1, PRDM16 and PGC1α) in it. In addition, BAT transplantation promoted the eWAT expression of various genes involved in fatty acid oxidation (such as Elvol3 and Tfam,). In contrast, extirpation of the interscapular BAT exacerbated HFD-induced obesity, insulin resistance and adipose tissue inflammation (by increasing M1 macrophages, CD8a T-cell and decreasing Tregs in eWAT). Taken together, our results suggested an important role of BAT in combating obesity-associated metabolic complications. These results open a novel therapeutic option to target obesity and related metabolic disorders like type 2 diabetes.