IL-15 is required for postexercise induction of the pro-oxidative mediators PPAR? and SIRT1 in male mice.

ABSTRACT: Physical exercise induces transient upregulation of the pro-oxidative mediators peroxisome proliferator-activated receptor-? (PPAR?), silent information regulator of transcription (sirtuin)-1 (SIRT1), PPAR? coactivator 1? (PGC-1?), and PGC-1? in skeletal muscle. To determine the role of the cytokine IL-15 in acute postexercise induction of these molecules, expression of these factors after a bout of exhaustive treadmill running was examined in the gastrocnemius muscle of untrained control and IL-15-knockout (KO) mice. Circulating IL-15 levels increased transiently in control mice after exercise. Control mice, but not IL-15-KO mice, upregulated muscle PPAR? and SIRT1 protein after exercise, accompanied by a complex pattern of mRNA expression for these factors. However, in exhaustive exercise, control mice ran significantly longer than IL-15-KO mice. Therefore, in a second experiment, mice were limited to a 20-minute run, after which a similar pattern of induction of muscle PPAR? and SIRT1 protein by control mice only was observed. In a separate experiment, IL-15-KO mice injected systemically with recombinant IL-15 upregulated muscle PPAR? and SIRT1 mRNA within 30 minutes and also exhibited increased muscle PPAR? protein levels by 3 hours. After exercise, both control and IL-15-KO mice downregulated IL-15 receptor-? (IL-15R?) mRNA, whereas IL-15R?-deficient mice exhibited constitutively elevated circulating IL-15 levels. These observations indicate IL-15 release after exercise is necessary for induction of PPAR? and SIRT1 at the protein level in muscle tissue and suggest that exercise releases IL-15 normally sequestered by the IL-15R? in the resting state. These findings could be used to develop an IL-15-based strategy to induce many of the metabolic benefits of physical exercise.

SUBMITTER: Quinn LS 

PROVIDER: S-EPMC5378429 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature