Zabielski, Piotrek

Omega‐3 polyunsaturated fatty acids (n‐3 PUFAs) protect insulin sensitivity and glucose homeostasis in rodent models of insulin resistance. These effects of n‐3 PUFAs are linked with anti‐inflammatory properties, but emerging data suggests that mechanisms may also converge on mitochondria. We evaluated the influence of dietary n‐3 PUFAs on mitochondrial physiology in the context of high‐fat diet (HFD) in mice. We hypothesized that the insulin‐sensitizing effects of n‐3 PUFAs would be accompanied by enhanced mitochondrial function in skeletal muscle, leading to attenuated levels of lipid metabolites known to interfere with insulin signaling. We fed mice HFD with or without fish oil for 10 weeks. HFD decreased glucose tolerance, but not in the presence of fish oil. Skeletal muscle long chain acyl coenzyme‐As and ceramides were significantly elevated with HFD, but attenuated in the presence of fish oil. Mitochondrial oxidative capacity was similarly increased in mice fed HFD with and without fish oil. These results indicate that n‐3 PUFAs protect insulin sensitivity, in part, by preventing the accumulation of lipid intermediated that interfere with insulin action. Furthermore, the respiratory function of skeletal muscle mitochondria does not appear to be a major factor in ectopic lipid accumulation, diet‐induced insulin resistance, or the protective effects of n‐3 PUFAs on insulin sensitivity.