Investigating IL-15 Metabolic Impact and Its Mechanism of Action in Skeletal Muscle Cells

dc.contributor.authorNadeau, Lucien
dc.description.abstractSkeletal muscle secretes many signalisation proteins named myokines. These myokines act as hormones and induce metabolic changes throughout the whole body to facilitate adaptation to physical exercise. Interleukin-15 (IL-15) is highly expressed in skeletal muscle and appears to influence many metabolic parameters that are defective in metabolic pathologies such as insulin resistance. For instance, IL-15 increases glucose uptake in muscle and whole-body fatty acid oxidation and its overexpression in skeletal muscle in mice generates a very lean and active phenotype. However, there are discordant reports throughout scientific literature. The aim of the current study was to 1) characterize the metabolic effects of IL-15 in L6 myotubes to determine whether L6 is a good model to study IL-15 and 2) to determine whether IL-15 activates the AMPK signaling. L6 myotubes were exposed to different concentrations of IL-15 and different metabolic parameters were assayed namely; oxygen consumption, glucose uptake, fatty acid oxidation, Glucose transporter 4 (GLUT4) translocation, oxidative phosphorylation (OXPHOS) complexes protein expression, troponin T expression and Akt, AMPK and Acetyl-CoA Carboxylase (ACC) phosphorylation state. Acute IL-15 treatment increased glucose uptake without activating insulin signaling pathway or GLUT4 translocation. Furthermore, acute IL-15 treatment increased resting oxygen consumption rate (OCR) while chronic IL-15 treatment also increased mitochondrial spare capacity, suggesting an increased mitochondrial biogenesis. IL-15 induced ACC phosphorylation in a dose-dependent manner and tended to increase AMPK phosphorylation but it did not reach statistical significance. Lastly, IL-15 did not influence troponin T state. Altogether, the present study demonstrates that L6 myotubes do not express all the pro-oxidative qualities of IL-15 reported by scientific literature. Nonetheless, IL-15 induces certain pro-oxidative metabolic effect that could help people living with obesity and diabetes.
dc.publisherUniversité d'Ottawa / University of Ottawa
dc.titleInvestigating IL-15 Metabolic Impact and Its Mechanism of Action in Skeletal Muscle Cells
dc.contributor.supervisorHarper, Mary-Ellen
dc.contributor.supervisorAguer, Célineédecine / Medicine
uottawa.departmentBiochimie, microbiologie et immunologie / Biochemistry, Microbiology and Immunology
CollectionThèses, 2011 - // Theses, 2011 -