Obesity Impairs Skeletal Muscle Regeneration Through Inhibition of AMPK

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • AMP-Activated Protein Kinases / genetics*
  • AMP-Activated Protein Kinases / metabolism
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Diet, High-Fat
  • Flow Cytometry
  • Hypoglycemic Agents / pharmacology
  • Immunoblotting
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Muscle Development / drug effects
  • Muscle Development / genetics*
  • Muscle, Skeletal / injuries
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiology
  • Obesity / metabolism*
  • Regeneration / drug effects
  • Regeneration / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonucleotides / pharmacology
  • Satellite Cells, Skeletal Muscle / metabolism*
  • Satellite Cells, Skeletal Muscle / transplantation


  • Hypoglycemic Agents
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • AMPK alpha1 subunit, mouse
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide