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

• Main Author: Nadeau, Lucien
• Other Authors: Harper, Mary-Ellen
• Language: en
• Published: Université d'Ottawa / University of Ottawa 2017
• Subjects: Metabolism; Myokines; IL-15; Muscle
• Online Access: http://hdl.handle.net/10393/36054; http://dx.doi.org/10.20381/ruor-20334

Skeletal 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.