Influence of fish oil on skeletal muscle mitochondrial energetics and lipid metabolites during high-fat diet

Am J Physiol Endocrinol Metab. 2013 Jun 15;304(12):E1391-403. doi: 10.1152/ajpendo.00584.2012. Epub 2013 Apr 30.


Omega-3 polyunsaturated fatty acids (n-3 PUFAs) enhance insulin sensitivity and glucose homeostasis in rodent models of insulin resistance. These beneficial effects have been linked with anti-inflammatory properties, but emerging data suggest that the mechanisms may also converge on mitochondria. We evaluated the influence of dietary n-3 PUFAs on mitochondrial physiology and muscle lipid metabolites in the context of high-fat diet (HFD) in mice. Mice were fed control diets (10% fat), HFD (60% fat), or HFD with fish oil (HFD+FO, 3.4% kcal from n-3 PUFAs) for 10 wk. Body mass and fat mass increased similarly in HFD and HFD+FO, but n-3 PUFAs attenuated the glucose intolerance that developed with HFD and increased expression of genes that regulate glucose metabolism in skeletal muscle. Despite similar muscle triglyceride levels in HFD and HFD+FO, long-chain acyl-CoAs and ceramides were lower in the presence of fish oil. Mitochondrial abundance and oxidative capacity were similarly increased in HFD and HFD+FO compared with controls. Hydrogen peroxide production was similarly elevated in HFD and HFD+FO in isolated mitochondria but not in permeabilized muscle fibers, likely due to increased activity and expression of catalase. These results support a hypothesis that n-3 PUFAs protect glucose tolerance, in part by preventing the accumulation of bioactive lipid mediators that interfere with insulin action. Furthermore, the respiratory function of skeletal muscle mitochondria does not appear to be a major factor in sphingolipid accumulation, glucose intolerance, or the protective effects of n-3 PUFAs.

Keywords: ceramide; essential fatty acids; fish oil; high-fat diet; insulin sensitivity; long-chain acyl-coenzyme A; mitochondria; omega-3 fatty acids; polyunsaturated fatty acids; sphingolipid.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Body Weight / physiology
  • Diet, High-Fat
  • Dietary Fats / pharmacology
  • Energy Metabolism / drug effects*
  • Energy Metabolism / physiology
  • Fish Oils / pharmacology*
  • Glucose Intolerance / metabolism
  • Lipid Metabolism / drug effects*
  • Lipid Metabolism / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Random Allocation


  • Dietary Fats
  • Fish Oils