Document Type
Article
Publication Date
2016
Abstract
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 aforementionedmRNA levels except for PGC1𝛽 andNrf1.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.
Recommended Citation
Thornton SM, Krolopp JE, Abbott MJ. IL-15 mediates mitochondrial activity through a PPARδ-dependent-PPARα-independent mechanism in skeletal muscle cells. PPAR Research. 2016;2016:5465804. doi:10.1155/2016/5465804.
Peer Reviewed
1
Copyright
The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
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Biomechanics Commons, Cell Biology Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Anatomy Commons, Medical Cell Biology Commons, Medical Genetics Commons, Musculoskeletal, Neural, and Ocular Physiology Commons, Musculoskeletal System Commons, Other Kinesiology Commons, Other Medical Sciences Commons, Other Medicine and Health Sciences Commons, Physiological Processes Commons
Comments
This article was originally published in PPAR Research in 2016. DOI: 10.1155/2016/5465804