PPAR gamma coactivator-1 alpha contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans Article

International Collaboration

cited authors

  • Koves, Timothy R., Sparks, Lauren M., Kovalik, J. P., Mosedale, Merrie, Arumugam, Ramamani, DeBalsi, Karen L., Everingham, Karen, Thorne, Leigh, Phielix, Esther, Meex, Ruth C., Kien, C. Lawrence, Hesselink, Matthijs K. C., Schrauwen, Patrick, Muoio, Deborah M.

funding text

  • This work was supported by National Institutes of Health Grants R01-AG-028930 (D. M.) and R01-DK-073284 (L. K. and D. M.); the American Diabetes Association (D. M.); Ellison Medical Foundation Grant AG-NS-0548-09 (T. K.); Dutch Diabetes Research Foundation Grant 2004.00.059; and VICI Grants 918.96.618 (P. S.) and 917.66.359 (M. H.) for innovative research from the Netherlands Organization for Scientific Research (NWO). The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

abstract

  • Intramuscular accumulation of triacylglycerol, in the form of lipid droplets (LD), has gained widespread attention as a hallmark of metabolic disease and insulin resistance. Paradoxically, LDs also amass in muscles of highly trained endurance athletes who are exquisitely insulin sensitive. Understanding the molecular mechanisms that mediate the expansion and appropriate metabolic control of LDs in the context of habitual physical activity could lead to new therapeutic opportunities. Herein, we show that acute exercise elicits robust upregulation of a broad program of genes involved in regulating LD assembly, morphology, localization, and mobilization. Prominent among these was perilipin-5, a scaffolding protein that affects the spatial and metabolic interactions between LD and their surrounding mitochondrial reticulum. Studies in transgenic mice and primary human skeletal myocytes established a key role for the exercise-responsive transcriptional coactivator PGC-1 alpha in coordinating intramuscular LD programming with mitochondrial remodeling. Moreover, translational studies comparing physically active versus inactive humans identified a remarkably strong association between expression of intramuscular LD genes and enhanced insulin action in exercise-trained subjects.(jlr) These results reveal an intimate molecular connection between intramuscular LD biology and mitochondrial metabolism that could prove relevant to the etiology and treatment of insulin resistance and other disorders of lipid imbalance.-Koves, T. R., L. M. Sparks, J. P. Kovalik, M. Mosedale, R. Arumugam, K. L. DeBalsi, K. Everingham, L. Thorne, E. Phielix, R. C. Meex, C. L. Kien, M. K. C. Hesselink, P. Schrauwen, and D. M. Muoio. PPAR gamma coactivator-1 alpha contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans. J. Lipid Res. 2013. 54: 522-534.

authors

Publication Date

  • February 1, 2013

webpage

published in

category

start page

  • 522

end page

  • 534

volume

  • 54

issue

  • 2

WoS Citations

  • 57

WoS References

  • 58