Fish oil protects against diet‐induced insulin resistance and modifies ceramide composition and mitochondrial physiology in skeletal muscle

Abstract

Omega3 fatty acids (EPA, DHA) have documented health benefits, including protection from development of insulin resistance. We investigated how fish oil affects muscle mitochondrial function and ceramide content as potential mechanisms of these insulin sensitizing effects. Mice were fed for 10 weeks with normal fat diet (NFD, 10% fat), high fat diet (HFD, 60% fat), or high fat diet + fish oil (HFD+N3, 60% fat with 3.4% kcals from DHA & EPA). Glucose tolerance (OGTT) significantly declined in HFD but not HFD+N3. Quadriceps muscle oxidative capacity (high-resolution respirometry) was significantly higher in HFD and HFD+N3 compared to NFD. Respiratory control ratios and P:O measurements indicated greater mitochondrial efficiency in HFD compared to NFD or HFD+N3. H2O2 production (Amplex Red) and NADPH oxidase activity (lucigenin) were similarly elevated in HFD and HFD+N3 compared to NFD. Total ceramide content (mass spectrometry) was higher in HFD and HFD+N3 groups in muscle homogenates, sarcoplasmic and myofibrillar fractions, but not in mitochondrial fractions. Analysis of ceramide composition revealed that the unsaturation index was higher in HFD, but similar in NFD and HFD+N3 in all cellular fractions. Our data indicate that DHA+EPA protect against HFD-induced glucose intolerance and also decrease mitochondrial coupling possibly through changes in the unsaturation of ceramides in skeletal muscle.