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Mitochondrial lipid oxidation is impaired in cultured myotubes from obese humans

International Journal of Obesity volume 36, pages 1025–1031 (2012)Cite this article

Subjects

Abstract

Objective:

The skeletal muscle of obese humans is characterized by an inability to appropriately respond to alterations in substrate availability. The purpose of this study was to determine if this metabolic inflexibility with obesity is retained in mitochondria of human skeletal muscle cells raised in culture (HSkMC) and to identify potential mechanisms involved.

Design:

Mitochondrial respiration was measured in permeabilized myotubes cultured from lean and obese individuals before and after a 24-h lipid incubation.

Results:

Mitochondrial respiration (state 3) in the presence of lipid substrate (palmitoyl carnitine) increased by almost twofold after lipid incubation in HSkMC from lean, but not obese subjects, indicative of metabolic inflexibility with obesity. The 24-h lipid incubation increased mitochondrial DNA (mtDNA) copy number in HSkMC from lean subjects by +16% (P<0.05); conversely, mtDNA copy number decreased in myotubes cultured from obese individuals (−13%, P=0.06). When respiration data were normalized to mtDNA copy number and other indices of mitochondrial content (COX-IV protein content and CS activity), the significant treatment effects of lipid incubation persisted in the lean subjects, suggesting concomitant alterations in mitochondrial function; no similar adjustment was evident in HSkMC from obese individuals.

Conclusion:

These data indicate that the skeletal muscle of obese individuals inherently lacks metabolic flexibility in response to lipid exposure, which consists of an inability to increase mitochondrial respiration in the presence of lipid substrate and perhaps by an inability to induce mitochondrial proliferation.

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Acknowledgements

This work was supported by NIH Grants AG025205 and DK56112 (to JAH) and DK073488 (to PDN).

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Authors and Affiliations

  1. The Human Performance Laboratory, East Carolina University, Greenville, NC, USA

    K E Boyle, D Zheng, P D Neufer & J A Houmard

  2. Department of Kinesiology, East Carolina University, Greenville, NC, USA

    K E Boyle, D Zheng, P D Neufer & J A Houmard

  3. The East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA

    K E Boyle, D Zheng, E J Anderson, P D Neufer & J A Houmard

  4. Department of Cardiovascular Sciences, East Carolina University, Greenville, NC, USA

    E J Anderson & P D Neufer

  5. The East Carolina Heart Institute, East Carolina University, Greenville, NC, USA

    E J Anderson

  6. Department of Physiology, East Carolina University, Greenville, NC, USA

    P D Neufer

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Correspondence to K E Boyle.

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Boyle, K., Zheng, D., Anderson, E. et al. Mitochondrial lipid oxidation is impaired in cultured myotubes from obese humans. Int J Obes 36, 1025–1031 (2012). https://doi.org/10.1038/ijo.2011.201

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  • DOI: https://doi.org/10.1038/ijo.2011.201

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