Exercise- And Training-Induced Upregulation of Skeletal Muscle Fatty Acid Oxidation Are Not Solely Dependent on Mitochondrial Machinery and Biogenesis

J Physiol. 2013 Sep 15;591(18):4415-26. doi: 10.1113/jphysiol.2012.238451. Epub 2012 Aug 13.


Regulation of skeletal muscle fatty acid oxidation (FAO) and adaptation to exercise training have long been thought to depend on delivery of fatty acids (FAs) to muscle, their diffusion into muscle, and muscle mitochondrial content and biochemical machinery. However, FA entry into muscle occurs via a regulatable, protein-mediated mechanism, involving several transport proteins. Among these CD36 is key. Muscle contraction and pharmacological agents induce CD36 to translocate to the cell surface, a response that regulates FA transport, and hence FAO. In exercising CD36 KO mice, exercise duration (-44%), and FA transport (-41%) and oxidation (-37%) are comparably impaired, while carbohydrate metabolism is augmented. In trained CD36 KO mice, training-induced upregulation of FAO is not observed, despite normal training-induced increases in mitochondrial density and enzymes. Transfecting CD36 into sedentary WT muscle (+41%), comparable to training-induced CD36 increases (+44%) in WT muscle, markedly upregulates FAO to rates observed in trained WT mice, but without any changes in mitochondrial density and enzymes. Evidently, in vivo CD36-mediated FA transport is key for muscle fuel selection and training-induced FAO upregulation, independent of mitochondrial adaptations. This CD36 molecular mechanism challenges the view that skeletal muscle FAO is solely regulated by muscle mitochondrial content and machinery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CD36 Antigens / metabolism
  • Exercise*
  • Fatty Acids / metabolism*
  • Humans
  • Mitochondria / metabolism*
  • Mitochondrial Turnover
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiology
  • Oxidation-Reduction*
  • Physical Exertion*


  • CD36 Antigens
  • Fatty Acids