IL-15 Mediates Mitochondrial Activity through a PPAR δ -Dependent-PPAR α -Independent Mechanism in Skeletal Muscle Cells

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 pparα and/or pparδ 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 pparα inhibitor (gw-6471),a pparδ inhibitor (gsk-3787),or both il-15 and the inhibitors. il-15 increased mitochondrial activity and induced pparα,pparδ,pgc1α,pgc1β,ucp2,and nrf1 expression. there was no effect of inhibiting pparα,in combination with il-15,on the aforementioned mrna levels except for pgc1β and nrf1. however,with pparδ inhibition,il-15 failed to induce the expression levels of pgc1α,pgc1β,ucp2,and nrf1. further,inhibition of pparδ 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 pparδ activity is required for the beneficial metabolic effects of il-15 signaling in skm. � 2016 shanta� m. thornton et al.