Molecular mediators of metabolic processes， to increase energy expenditure， have become a focus for therapies of obesity. The discovery of cytokines secreted from the skeletal muscle (SKM)， termed "myokines，" has garnered attention due to their positive effects on metabolic processes. Interleukin-15 (IL-15) is a myokine that has numerous positive metabolic effects and is linked to the PPAR family of mitochondrial regulators. Here， we aimed to determine the importance of PPAR and/or PPAR as targets of IL-15 signaling. C2C12 SKM cells were differentiated for 6 days and treated every other day with IL-15 (100 ng/mL)， a PPAR inhibitor (GW-6471)， a PPAR inhibitor (GSK-3787)， or both IL-15 and the i... More
Molecular mediators of metabolic processes， to increase energy expenditure， have become a focus for therapies of obesity. The discovery of cytokines secreted from the skeletal muscle (SKM)， termed "myokines，" has garnered attention due to their positive effects on metabolic processes. Interleukin-15 (IL-15) is a myokine that has numerous positive metabolic effects and is linked to the PPAR family of mitochondrial regulators. Here， we aimed to determine the importance of PPAR and/or PPAR as targets of IL-15 signaling. C2C12 SKM cells were differentiated for 6 days and treated every other day with IL-15 (100 ng/mL)， a PPAR inhibitor (GW-6471)， a PPAR inhibitor (GSK-3787)， or both IL-15 and the inhibitors. IL-15 increased mitochondrial activity and induced PPAR， PPAR， PGC1， PGC1， UCP2， and Nrf1 expression. There was no effect of inhibiting PPAR， in combination with IL-15， on the aforementioned mRNA levels except for PGC1 and Nrf1. However， with PPAR inhibition， IL-15 failed to induce the expression levels of PGC1， PGC1， UCP2， and Nrf1. Further， inhibition of PPAR abolished IL-15 induced increases in citrate synthase activity， ATP production， and overall mitochondrial activity. IL-15 had no effects on mitochondrial biogenesis. Our data indicates that PPAR activity is required for the beneficial metabolic effects of IL-15 signaling in SKM.
