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Item Open Access Regulation of Skeletal Muscle Glucose and Fat Metabolism by DHA and EPA(2019-11-22) Katsnelson, Glen; Ceddia, RolandoThis study investigated whether docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids can directly regulate glucose and fat metabolism in skeletal muscle, besides exerting anti-inflammatory effects. To accomplish this, L6 skeletal muscle cells were treated with 50M of either DHA or EPA for 1, 3, and 5 days. We found that glucose uptake and glycogen synthesis as well as AKT and GSK3 phosphorylation remained unaffected. However, glucose and palmitate oxidation rates were consistently increased (day 1-5) by DHA treatment, whereas EPA increased this variable transiently (day 1). Similarly, only DHA caused significant and sustained increases in AMPK phosphorylation and contents of CPT1b and PGC-1. DHA also had a more potent anti-inflammatory effect than EPA. In conclusion, besides exerting anti-inflammatory effects, EPA, and to a greater extent, DHA, directly regulated glucose and fat metabolism in skeletal muscle cells. Thus, by directly enhancing glucose and fat oxidation, DHA may protect skeletal muscle against lipotoxicity.