Lipid-induced mitochondrial stress and insulin action in muscle

Cell Metab. 2012 May 2;15(5):595-605. doi: 10.1016/j.cmet.2012.04.010.


The interplay between mitochondrial energetics, lipid balance, and muscle insulin sensitivity has remained a topic of intense interest and debate for decades. One popular view suggests that increased oxidative capacity benefits metabolic wellness, based on the premise that it is healthier to burn fat than glucose. Attempts to test this hypothesis using genetically modified mouse models have produced contradictory results and instead link muscle insulin resistance to excessive fat oxidation, acylcarnitine production, and increased mitochondrial H(2)O(2)-emitting potential. Here, we consider emerging evidence that insulin action in muscle is driven principally by mitochondrial load and redox signaling rather than oxidative capacity.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Insulin / metabolism*
  • Insulin / pharmacology
  • Lipid Metabolism*
  • Mice
  • Mitochondria / metabolism*
  • Mitochondria, Muscle / metabolism*
  • Oxidative Stress


  • Insulin