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    Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system

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    Author
    Kovalik, Jean-Paul; Slentz, Dorothy; Stevens, Robert D.; Kraus, William E.; Houmard, Joseph A.; Nicoll, James B.; Lea-Currie, Y. Renee; Everingham, Karen; Kien, C. Lawrence; Buehrer, Benjamin M.; Muoio, Deborah M.
    Abstract
    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. 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. 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. 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.
    URI
    http://hdl.handle.net/10342/7743
    Date
    2011-06-20
    Citation:
    APA:
    Kovalik, Jean-Paul, & Slentz, Dorothy, & Stevens, Robert D., & Kraus, William E., & Houmard, Joseph A., & Nicoll, James B., & Lea-Currie, Y. Renee, & Everingham, Karen, & Kien, C. Lawrence, & Buehrer, Benjamin M., & Muoio, Deborah M.. (June 2011). Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system. Diabetes, (60:7), p.1882 - 1893. Retrieved from http://hdl.handle.net/10342/7743

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    MLA:
    Kovalik, Jean-Paul, and Slentz, Dorothy, and Stevens, Robert D., and Kraus, William E., and Houmard, Joseph A., and Nicoll, James B., and Lea-Currie, Y. Renee, and Everingham, Karen, and Kien, C. Lawrence, and Buehrer, Benjamin M., and Muoio, Deborah M.. "Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system". Diabetes. 60:7. (1882 - 1893.), June 2011. July 07, 2022. http://hdl.handle.net/10342/7743.
    Chicago:
    Kovalik, Jean-Paul and Slentz, Dorothy and Stevens, Robert D. and Kraus, William E. and Houmard, Joseph A. and Nicoll, James B. and Lea-Currie, Y. Renee and Everingham, Karen and Kien, C. Lawrence and Buehrer, Benjamin M. and Muoio, Deborah M., "Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system," Diabetes 60, no. 7 (June 2011), http://hdl.handle.net/10342/7743 (accessed July 07, 2022).
    AMA:
    Kovalik, Jean-Paul, Slentz, Dorothy, Stevens, Robert D., Kraus, William E., Houmard, Joseph A., Nicoll, James B., Lea-Currie, Y. Renee, Everingham, Karen, Kien, C. Lawrence, Buehrer, Benjamin M., Muoio, Deborah M.. Metabolic remodeling of human skeletal myocytes by cocultured adipocytes depends on the lipolytic state of the system. Diabetes. June 2011; 60(7) 1882 - 1893. http://hdl.handle.net/10342/7743. Accessed July 07, 2022.
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