title: IL-15 overexpression promotes endurance, oxidative energy metabolism, and muscle PPARδ, SIRT1, PGC-1α, and PGC-1β expression in male mice.
abstract: Endurance exercise initiates a pattern of gene expression that promotes fat oxidation, which in turn improves endurance, body composition, and insulin sensitivity. The signals from exercise that initiate these pathways have not been completely characterized. IL-15 is a cytokine that is up-regulated in skeletal muscle after exercise and correlates with leanness and insulin sensitivity. To determine whether IL-15 can induce any of the metabolic adaptations associated with exercise, substrate metabolism, endurance, and molecular expression patterns were examined in male transgenic mice with constitutively elevated muscle and circulating IL-15 levels. IL-15 transgenic mice ran twice as long as littermate control mice in a run-to-exhaustion trial and preferentially used fat for energy metabolism. Fast muscles in IL-15 transgenic mice exhibited high expression of intracellular mediators of oxidative metabolism that are induced by exercise, including sirtuin 1, peroxisome proliferator-activated receptor (PPAR)-δ, PPAR-γ coactivator-1α, and PPAR-γ coactivator-1β. Muscle tissue in IL-15 transgenic mice exhibited myosin heavy chain and troponin I mRNA isoform expression patterns indicative of a more oxidative phenotype than controls. These findings support a role for IL-15 in induction of exercise endurance, oxidative metabolism, and skeletal muscle molecular adaptations induced by physical training.
authors.affiliation: S-182 Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, 1660 South Columbian Way, Seattle, WA 98108, USA. quinnL@uw.edu
authors.forename: Lebris S
authors.initials: LS
authors.lastname: Quinn
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Anderson
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Conner
authors.forename: Tami
authors.initials: T
authors.lastname: Wolden-Hanson
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D019409:Interleukin-15 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics; D047494:PPAR delta / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D056564:Sirtuin 1 / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D019210:Troponin I / Q000235:genetics
chemical_list: D019409:Interleukin-15; D047494:PPAR delta; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D019210:Troponin I; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D018995:Myosin Heavy Chains