Eicosapentaenoic acid reduces high‐fat diet‐induced insulin resistance by altering adipose tissue glycolytic and inflammatory function (383.8)

Abstract

We previously reported Eicosapentaenoic Acid (EPA)'s ability to prevent high‐fat (HF) diet‐induced obesity, insulin resistance, and inflammation. In this study, we dissected mechanisms mediating anti‐inflammatory and anti‐lipogenic actions of EPA, using histology/ immunohistochemistry, transcriptomic and energetic analyses of adipose tissues from HF and HF‐EPA fed mice, or 3T3‐L1 adipocytes treated with or without EPA. Microarray and real time PCR analyses of adipose tissue from these mice showed that EPA decreased expression of genes associated with cell proliferation, apoptosis, adipogenesis and glucose metabolism (namely Fasn, Srebf1, Cebpa, Ncoa2, and Axin1). Preliminary extracellular flux studies indicate changes in glycolysis in differentiated 3T3‐L1 adipocytes treated with EPA, compared to those treated with palmitic acid (PA) alone or with EPA. These results are consistent with increased fatty acid oxidation‐related metabolites in gonadal fat after EPA supplementation. Histology and immunohistochemistry results showed a significantly lower mean adipocyte size and macrophage infiltration in mice fed a HF‐EPA diet vs. HF, indicating that EPA prevented HF‐diet induced adipocyte inflammation and hypertrophy. In conclusion, our studies demonstrate that EPA ameliorates glucose homeostasis at least in part by reducing adipose tissue inflammation, glycolysis and lipid accumulation.Grant Funding Source: USDA, AHA and TTU (COHS and OVPR)