Enhancement of muscle mitochondrial oxidative capacity and alterations in insulin action are lipid species-dependent: Potent tissue-specific effects of medium chain fatty acids

  1. Nigel Turner (n.turner{at},2,
  2. Krit Hariharan1,
  3. Jennifer TidAng1,
  4. Georgia Frangioudakis1,
  5. Susan M. Beale1,
  6. Lauren E. Wright1,
  7. Xiao Yi Zeng1,
  8. Simon J. Leslie1,
  9. Jing-Ya Li1,3,
  10. Edward W. Kraegen1,4,
  11. Gregory J. Cooney1,2 and
  12. Ji-Ming Ye1
  1. 1Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
  2. 2St Vincent's Hospital Clinical School, University of New South Wales, Sydney, NSW, Australia
  3. 3Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
  4. 4School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia


    Objective: Medium-chain fatty acids (MCFA) have been reported to be less obesogenic than long-chain fatty acids (LCFA), however relatively little is known regarding their effect on insulin action. Here we examined the tissue-specific effects of MCFA on lipid metabolism and insulin action.

    Methods: C57BL6/J mice and Wistar rats were fed either a low-fat (LF) control diet or high-fat diets rich in MCFA or LCFA for 4-5 weeks and markers of mitochondrial oxidative capacity, lipid levels and insulin action were measured.

    Results: Mice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals. In skeletal muscle, triglyceride levels were increased by the LCFA diet (77%, P<0.01), but remained at LF control levels in the MCFA-fed animals. The LCFA-diet increased (20-50%, P<0.05) markers of mitochondrial metabolism in muscle compared to LF controls, however the increase in oxidative capacity was substantially greater in MCFA-fed animals (50-140% vs. LF controls, P<0.01). The MCFA diet induced a greater accumulation of liver triglycerides than the LCFA diet, likely due to an upregulation of several lipogenic enzymes. In rats, isocaloric feeding of MCFA or LCFA HF diets induced hepatic insulin resistance to a similar degree, however insulin action was preserved at the level of LF controls in muscle and adipose from MCFA-fed animals.

    Conclusions: MCFA reduce adiposity and preserve insulin action in muscle and adipose, despite inducing steatosis and insulin resistance in the liver. Dietary supplementation with MCFA may therefore be beneficial for preventing obesity and peripheral insulin resistance.


      • Received May 26, 2009.
      • Accepted August 4, 2009.

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    1. Diabetes
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