Eicosapentaenoic acid regulates brown adipose tissue gene expression and metabolism in high fat fed mice (1037.5)

Abstract

Brown adipose tissue (BAT) is a thermogenic tissue, a key regulator of energy balance and a potential therapeutic target for obesity. We previously reported that eicosapentaenoic acid (EPA) reduced high fat (HF) diet‐induced obesity and insulin resistance in mice, independent of energy intake. We hypothesized that these effects are mediated in part by BAT thermogenesis. Using mice fed HF or HF‐EPA diets for 11 weeks, we demonstrated that BAT from HF‐EPA mice expressed higher mRNA levels of thermogenic genes such as fibronectin type lll domain containing 5 (FNDC5), peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1α) and uncoupling protein 3 (UCP3), compared to HF mice. EPA also induced expression of angiotensinogen (Agt) gene and other genes related to insulin sensitivity such as Glut 1 while downregulating arachidonate 5‐lipoxygenase (ALOX5), an inflammatory biomarker. At the protein level, EPA upregulated uncoupling protein (UCP) and downregulated fatty acid synthase (FAS). Thus, EPA exerts dual effects on adipose tissue depots, by reducing WAT inflammation and lipid accumulation, while activating BAT thermogenesis and reducing lipogenesis. In conclusion, EPA exerts differential tissue specific effects to reduce obesity‐associated metabolic disorders. Further molecular studies in cultured brown adipocytes are being conducted to dissect direct effects of EPA on brown fat.Grant Funding Source: Supported by AHA, USDA and TTU