Eicosapentaenoic acid Increases Brown Adipose Tissue Thermogenic Markers in High Fat Fed Mice

Abstract

Brown adipose tissue (BAT) converts excess food energy into thermal energy, and has therefore attracted attention as a new area of research to counter obesity. We previously reported that eicosapentaenoic acid (EPA) reduces high fat diet-induced obesity and insulin resistance in mice, independent of energy intake; however, the role of EPA in regulating thermogenesis in brown fat is not well understood. Hence, we hypothesize that EPA induces thermogenesis in brown fat to counteract obesity and insulin resistance. To test our hypothesis, C57BL/6J mice fed with high fat (HF) with or without EPA were used. BAT from HF-EPA mice expressed higher mRNA levels of thermogenic genes such as FNDC5 and PGC1-alpha, compared to HF mice. Furthermore, EPA up-regulated uncoupling protein 1 (UCP-1) protein content in BAT. Another key marker for brown fat thermogenesis, PRDM16, was also significantly higher in EPA fed mice vs HF, confirming thermogenesis induction. To further study direct effects of EPA on BAT, a clonal brown fat cell line, HIB1, was treated with different doses of EPA. Mitochondrial content measured using a MitoTracker was dose-dependently and significantly higher in EPA treated vs. vehicle, suggesting higher mitochondrial activity in EPA treated cells. Currently, cell and molecular studies are underway to determine mechanisms mediating EPA effects on brown adipocyte metabolism and mitochondrial function. In conclusion, our results from in vivo and in vitro studies indicate that EPA reduces obesity and its associated metabolic disorders at least in part by activating BAT thermogenesis. Supported by AHA, USDA and TTU