Reduced exercise endurance in interleukin-6-deficient mice

Endocrinology. 2004 Jun;145(6):2680-6. doi: 10.1210/en.2003-1319. Epub 2004 Feb 26.


IL-6 is produced and released in large amounts from skeletal muscle during prolonged exercise in both mice and humans, but there are few data indicating the biological significance of this. IL-6 exerts metabolic effects such as stimulating energy expenditure and reducing body fat mass. We have now investigated the effects of IL-6 deficiency on exercise endurance and energy expenditure in preobese and obese IL-6-deficient (IL-6(-/-)) mice. Four-month-old preobese and 7-month-old obese IL-6(-/-) male mice backcrossed to C57BL/6 and their littermate controls were exercised on a treadmill, and energy expenditure was measured as oxygen consumption with the use of indirect calorimetry. The preobese IL-6(-/-) mice were significantly leaner than the control mice, whereas the older IL-6(-/-) mice, as expected, had developed obesity. Resting young, but not older, IL-6(-/-) mice had an elevated respiratory exchange ratio (RER), indicating that they oxidize carbohydrates rather than fat for energy utilization. During exercise, the young and older IL-6(-/-) mice had a reduced endurance and a progressive decrease in oxygen consumption compared with control mice. There was no difference in RER in young IL-6(-/-) mice, whereas RER was enhanced in older IL-6(-/-), mice during exercise. In summary, IL-6(-/-) mice have reduced endurance and energy expenditure during exercise, suggesting that IL-6 is necessary for normal exercise capacity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Composition
  • Energy Metabolism
  • Glycogen / blood
  • Interleukin-6 / deficiency
  • Interleukin-6 / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity
  • Obesity / blood
  • Obesity / metabolism
  • Obesity / physiopathology*
  • Physical Endurance / physiology*
  • Pulmonary Gas Exchange


  • Interleukin-6
  • Glycogen