| Metabolic Remodeling of Human Skeletal Myocytes by Cocultured Adipocytes Depends on the Lipolytic State of the System. | |
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MedLine Citation:
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PMID: 21602515 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE Adipocyte infiltration of the musculoskeletal system is well recognized as a hallmark of aging, obesity, and type 2 diabetes. Intermuscular adipocytes might serve as a benign storage site for surplus lipid or play a role in disrupting energy homeostasis as a result of dysregulated lipolysis or secretion of proinflammatory cytokines. This investigation sought to understand the net impact of local adipocytes on skeletal myocyte metabolism. RESEARCH DESIGN AND METHODS Interactions between these two tissues were modeled using a coculture system composed of primary human adipocytes and human skeletal myotubes derived from lean or obese donors. Metabolic analysis of myocytes was performed after coculture with lipolytically silent or activated adipocytes, and included transcript and metabolite profiling along with assessment of substrate selection and insulin action. RESULTS Cocultured adipocytes increased myotube mRNA expression of genes involved in oxidative metabolism, regardless of the donor and degree of lipolytic activity. Adipocytes in the basal state sequestered free fatty acids, thereby forcing neighboring myotubes to rely more heavily on glucose fuel. Under this condition, insulin action was enhanced in myotubes from lean but not obese donors. In contrast, when exposed to lipolytically active adipocytes, cocultured myotubes shifted substrate use in favor of fatty acids, which was accompanied by intracellular accumulation of triacylglycerol and even chain acylcarnitines, decreased glucose oxidation, and modest attenuation of insulin signaling. CONCLUSIONS The effects of cocultured adipocytes on myocyte substrate selection and insulin action depended on the metabolic state of the system. These findings are relevant to understanding the metabolic consequences of intermuscular adipogenesis. |
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Authors:
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Jean-Paul Kovalik; Dorothy Slentz; Robert D Stevens; William E Kraus; Joseph A Houmard; James B Nicoll; Y Renee Lea-Currie; Karen Everingham; C Lawrence Kien; Benjamin M Buehrer; Deborah M Muoio |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-20 |
Journal Detail:
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Title: Diabetes Volume: - ISSN: 1939-327X ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372763 Medline TA: Diabetes Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, North Carolina. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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