Abstract

Eicosapentaenoic acid (EPA), an omega 3 fatty acid exerts potent anti‐inflammatory and hypolipidemic effects. We previously reported that mice fed high fat diets supplemented with EPA (HF‐EPA) were resistant to diet‐induced obesity, inflammation and insulin resistance. Here we further investigate both in vivo and in vitro the mechanisms by which muscle tissue contributes to the metabolic benefits of EPA. We compared changes in gene and protein expression and tissue metabolites in mice fed either HF or HF‐EPA for 11 weeks and in C2C12 cells treated with or without EPA. Docosahexaenoic acid, saturated fatty acids and cholesterol precursors were increased in muscle of mice fed HF‐EPA vs. HF. Surprisingly, EPA increased fatty acid oxidation in adipose tissue but not in muscle. To determine mechanisms mediating direct effects of EPA in muscle in vitro, we used the mouse myocyte cell line C2C12 cells. Consistent with our findings in vivo, treatment of C2C12 cells with 50μM EPA increased lipoprotein lipase (Lpl) gene expression in a time‐dependent manner while fatty acid oxidation was unchanged. In conclusion, high fat diets supplemented with EPA increased saturated fatty acids and cholesterol precursors content in muscle with no significant changes in fatty acid oxidation. These findings suggest a possible unique role of EPA in mediating muscle cholesterogenesis in mice.Grant Funding Source: Suported by USDA, AHA & TTU (COHS &OVPR)

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