| PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans. | |
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MedLine Citation:
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PMID: 23175776 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 that 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 co-activator, PGC-1α, 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. 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 other disorders of lipid imbalance. |
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Authors:
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Timothy R Koves; Lauren M Sparks; J P Kovalik; Merrie Mosedale; Ramamani Arumugam; Karen L Debalsi; Karen Everingham; Leigh Thorne; Esther Phielix; Ruth C Meex; C Lawrence Kien; Matthijs K C Hesselink; Patrick Schrauwen; Deborah M Muoio |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-21 |
Journal Detail:
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Title: Journal of lipid research Volume: - ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Duke University, United States; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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