IL-15Rα is a determinant of muscle fuel utilization, and its loss protects against obesity

Am J Physiol Regul Integr Comp Physiol. 2015 Oct 15;309(8):R835-44. doi: 10.1152/ajpregu.00505.2014. Epub 2015 Aug 12.


IL-15Rα is the widely expressed primary binding partner for IL-15. Because of the wide distribution in nonlymphoid tissues like skeletal muscle, adipose, or liver, IL-15/IL-15Rα take part in physiological and metabolic processes not directly related to immunity. In fast muscle, lack of IL-15Rα promotes an oxidative switch, with increased mitochondrial biogenesis and fatigue resistance. These effects are predicted to reproduce some of the benefits of exercise and, therefore, improve energy homeostasis. However, the direct effects of IL-15Rα on metabolism and obesity are currently unknown. We report that mice lacking IL-15Rα (IL-15Rα(-/-)) are resistant to diet-induced obesity (DIO). High-fat diet-fed IL-15Rα(-/-) mice have less body and liver fat accumulation than controls. The leaner phenotype is associated with increased energy expenditure and enhanced fatty acid oxidation by muscle mitochondria. Despite being protected against DIO, IL-15Rα(-/-) are hyperglycemic and insulin-resistant. These findings identify novel roles for IL-15Rα in metabolism and obesity.

Keywords: diet-induced obesity; fatigue recovery; fatty acid oxidation; glucose homeostasis; interleukin-15 receptor alpha; muscle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose
  • Body Composition
  • Body Temperature
  • Energy Metabolism / physiology*
  • Fatty Acids / metabolism
  • Gene Expression Regulation / physiology*
  • Glucose Tolerance Test
  • Homeostasis
  • Insulin / metabolism
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism*
  • Interleukin-15 Receptor alpha Subunit / genetics
  • Interleukin-15 Receptor alpha Subunit / metabolism*
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal / metabolism*
  • Obesity / genetics
  • Obesity / metabolism*
  • Thermography


  • Blood Glucose
  • Fatty Acids
  • Insulin
  • Interleukin-15
  • Interleukin-15 Receptor alpha Subunit