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Obesity impairs skeletal muscle AMPK signaling during exercise: role of AMPKα2 in the regulation of exercise capacity in vivo

International Journal of Obesity volume 35, pages 982–989 (2011)Cite this article

Subjects

Abstract

Objective:

Skeletal muscle AMP-activated protein kinase (AMPK)α2 activity is impaired in obese, insulin-resistant individuals during exercise. We determined whether this defect contributes to the metabolic dysregulation and reduced exercise capacity observed in the obese state.

Design:

C57BL/6J wild-type (WT) mice and/or mice expressing a kinase dead AMPKα2 subunit in skeletal muscle (α2-KD) were fed chow or high-fat (HF) diets from 3 to 16 weeks of age. At 15 weeks, mice performed an exercise stress test to determine exercise capacity. In WT mice, muscle glucose uptake and skeletal muscle AMPKα2 activity was assessed in chronically catheterized mice (carotid artery/jugular vein) at 16 weeks. In a separate study, HF-fed WT and α2-KD mice performed 5 weeks of exercise training (from 15 to 20 weeks of age) to test whether AMPKα2 is necessary to restore work tolerance.

Results:

HF-fed WT mice had reduced exercise tolerance during an exercise stress test, and an attenuation in muscle glucose uptake and AMPKα2 activity during a single bout of exercise (P<0.05 versus chow). In chow-fed α2-KD mice, running speed and time were impaired ∼45 and ∼55%, respectively (P<0.05 versus WT chow); HF feeding further reduced running time ∼25% (P<0.05 versus α2-KD chow). In response to 5 weeks of exercise training, HF-fed WT and α2-KD mice increased maximum running speed ∼35% (P<0.05 versus pre-training) and maintained body weight at pre-training levels, whereas body weight increased in untrained HF WT and α2-KD mice. Exercise training restored running speed to levels seen in healthy, chow-fed mice.

Conclusion:

HF feeding impairs AMPKα2 activity in skeletal muscle during exercise in vivo. Although this defect directly contributes to reduced exercise capacity, findings in HF-fed α2-KD mice show that AMPKα2-independent mechanisms are also involved. Importantly, α2-KD mice on a HF-fed diet adapt to regular exercise by increasing exercise tolerance, demonstrating that this adaptation is independent of skeletal muscle AMPKα2 activity.

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Acknowledgements

This work was supported by National Institutes of Health Grants U24 DK-59637 and R01 DK-54902 (to DHW). RS Lee-Young was supported by a Mentor-Based Fellowship from the American Diabetes Association.

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Author notes

  1. J E Ayala

    Present address: 3Current address: Diabetes and Obesity Research Center, Burnham Institute for Medical Research, FL, USA.,

  2. P T Fueger

    Present address: 4Current address: Department of Pediatrics, Department of Cellular and Integrative Physiology, and Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.,

Authors and Affiliations

  1. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA

    R S Lee-Young, J E Ayala, P T Fueger, W H Mayes, L Kang & D H Wasserman

  2. The Mouse Metabolic Phenotyping Center, Vanderbilt University School of Medicine, Nashville, TN, USA

    J E Ayala & D H Wasserman

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  1. R S Lee-Young
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Correspondence to R S Lee-Young.

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Lee-Young, R., Ayala, J., Fueger, P. et al. Obesity impairs skeletal muscle AMPK signaling during exercise: role of AMPKα2 in the regulation of exercise capacity in vivo. Int J Obes 35, 982–989 (2011). https://doi.org/10.1038/ijo.2010.220

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  • DOI: https://doi.org/10.1038/ijo.2010.220

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