title: IL-15 expression increased in response to treadmill running and inhibited endoplasmic reticulum stress in skeletal muscle in rats.
abstract: Interleukin 15 (IL-15) has recently been proposed as a circulating myokine involved in glucose uptake and utilization in skeletal muscle. However, the role and mechanism of IL-15 in exercise improving insulin resistance (IR) is unclear. Here, we investigated the alteration in expression of IL-15 and IL-15 receptor α (IL-15Rα) in skeletal muscle during treadmill running in rats with IR induced by a high-fat diet (HFD) and elucidated the mechanism of the anti-IR effects of IL-15. At 20 weeks of HFD, rats showed severe IR, with increased levels of fasting blood sugar and plasma insulin, impaired glucose tolerance, and reduced glucose transport activity. IL-15 immunoreactivity and mRNA level in gastrocnemius muscle were decreased markedly as compared with controls. IL-15Rα protein and mRNA levels in both soleus and gastrocnemius muscle were significantly decreased, which might attenuate the signaling or secretion of IL-15 in muscle. Eight-week treadmill running completely ameliorated HFD-induced IR and reversed the downregulated level of IL-15 and IL-15Rα in skeletal muscle of HFD-fed rats. To investigate whether IL-15 exerts its anti-IR effects directly in muscle, we pre-incubated muscle strips with the endoplasmic reticulum stress (ERS) inducer dithiothreitol (DTT) or tunicamycin (Tm); IL-15 treatment markedly decreased the protein expression of the ERS markers 78-kDa glucose-regulated protein, 94-kDa glucose-regulated protein and C/EBP homologous protein and inhibited ERS induced by DTT or Tm. Therefore, treadmill running promoted skeletal IL-15 and IL-15Rα expression in HFD-induced IR in rats. The inhibitory effect of IL-15 on ERS may be involved in improved insulin sensitivity with exercise training.
authors.affiliation: School of P.E. and Sports Science, Beijing Normal University, Beijing, 100875, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Yang
authors.forename: Li-Jie
authors.initials: LJ
authors.lastname: Luo
authors.forename: Wen-Jia
authors.initials: WJ
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Yong-Fen
authors.initials: YF
authors.lastname: Qi
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004229:Dithiothreitol / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D018149:Glucose Intolerance; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053647:Receptors, Interleukin-15 / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D007328:Insulin; D015848:Interleukin-5; D053647:Receptors, Interleukin-15; D014415:Tunicamycin; D004229:Dithiothreitol