Regulation of Skeletal Muscle Glucose and Fat Metabolism by DHA and EPA

This 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.