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Diabetes. 2016 Jan;65(1):188-200. doi: 10.2337/db15-0647. Epub 2015 Sep 17.

Obesity Impairs Skeletal Muscle Regeneration Through Inhibition of AMPK.

Author information

1
Washington Center for Muscle Biology, Department of Animal Sciences and Department of Pharmaceutical Sciences, Washington State University, Pullman, WA.
2
School of Food Science, Washington State University, Pullman, WA.
3
INSERM U1016, Institut Cochin, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France CNRS UMR 8104, Paris, France.
4
Washington Center for Muscle Biology, Department of Animal Sciences and Department of Pharmaceutical Sciences, Washington State University, Pullman, WA min.du@wsu.edu.

Abstract

Obesity is increasing rapidly worldwide and is accompanied by many complications, including impaired muscle regeneration. The obese condition is known to inhibit AMPK activity in multiple tissues. We hypothesized that the loss of AMPK activity is a major reason for hampered muscle regeneration in obese subjects. We found that obesity inhibits AMPK activity in regenerating muscle, which was associated with impeded satellite cell activation and impaired muscle regeneration. To test the mediatory role of AMPKα1, we knocked out AMPKα1 and found that both proliferation and differentiation of satellite cells are reduced after injury and that muscle regeneration is severely impeded, reminiscent of hampered muscle regeneration seen in obese subjects. Transplanted satellite cells with AMPKα1 deficiency had severely impaired myogenic capacity in regenerating muscle fibers. We also found that attenuated muscle regeneration in obese mice is rescued by AICAR, a drug that specifically activates AMPK, but AICAR treatment failed to improve muscle regeneration in obese mice with satellite cell-specific AMPKα1 knockout, demonstrating the importance of AMPKα1 in satellite cell activation and muscle regeneration. In summary, AMPKα1 is a key mediator linking obesity and impaired muscle regeneration, providing a convenient drug target to facilitate muscle regeneration in obese populations.

PMID:
26384382
PMCID:
PMC4686944
DOI:
10.2337/db15-0647
[Indexed for MEDLINE]
Free PMC Article

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