Anti‐inflammatory and metabolic mechanisms by which omega‐3 fatty acids improve insulin resistance in high fat diet‐induced obese mice

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In this study, we investigated the effects of eicosapentaenoic acid (EPA) on prevention (P) and reversal (R) of high‐fat (HF) diet‐induced obesity and metabolic alterations. Male C57BL/6J mice were fed low‐fat (LF), HF or a HF‐EPA‐P diet for 11 weeks. A fourth group was initially fed HF for 6 weeks followed by HF‐EPA‐R diet for 5 weeks. As expected, mice fed HF diet developed obesity and glucose intolerance. In contrast, mice fed HF‐EPA‐P diet maintained normal glucose tolerance despite weight gain when compared to the LF group. While the HF group developed fasting hyperglycemia and hyperinsulinemia, both HF‐EPA groups (P and R)‐R exhibited normal glycemia and insulinemia, demonstrating EPA's ability to prevent and improve insulin resistance associated with high fat feeding. Analysis of adipokines revealed that plasma adiponectin levels were lower in the HF group, but were comparable between LF and HF‐EPA groups, regardless of the high fat content of the diet. Further analysis of adipose tissue adipokine levels and proteomic studies in cultured adipocytes demonstrated that EPA reduces adipose inflammation (MCP‐1 and PAI‐1) and lipogenesis, while increasing fatty acid oxidation and mitochondrial content. These studies demonstrate that beneficial effects of EPA in improving insulin resistance are in part mediated by EPA's lipid oxidizing and anti‐inflammatory effects.Grant Funding Source: UT‐ORC, AHA and USDA‐NRI