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

ABSTRACT: IL-15R? 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-15R? take part in physiological and metabolic processes not directly related to immunity. In fast muscle, lack of IL-15R? 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-15R? on metabolism and obesity are currently unknown. We report that mice lacking IL-15R? (IL-15R?(-/-)) are resistant to diet-induced obesity (DIO). High-fat diet-fed IL-15R?(-/-) 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-15R?(-/-) are hyperglycemic and insulin-resistant. These findings identify novel roles for IL-15R? in metabolism and obesity.

SUBMITTER: Loro E 

PROVIDER: S-EPMC4631541 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature