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

Emanuele Loro, Erin L. Seifert, Cynthia Moffat, Freddy Romero, Manoj K. Mishra, Zheng Sun, Predrag Krajacic, Frederick Anokye-Danso, Ross S. Summer, Rexford S. Ahima, Tejvir S. Khurana

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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-1-) are resistant to diet-induced obesity (DIO). High-fat diet-fed IL-15Rα-1- 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-1- are hyperglycemic and insulin-resistant. These findings identify novel roles for IL-15Rα in metabolism and obesity.

Original languageEnglish (US)
Pages (from-to)R835-R844
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number8
StatePublished - 2015
Externally publishedYes


  • Diet-induced obesity
  • Fatigue recovery
  • Fatty acid oxidation
  • Glucose homeostasis
  • Interleukin-15 receptor alpha
  • Muscle

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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