The AMPK agonist 5‐aminoimidazole‐4‐carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation‐associated cachectic muscle wasting Journal Articles uri icon

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  • Activation of AMPK has been associated with pro-atrophic signaling in muscle. However, AMPK also has anti-inflammatory effects, suggesting that in cachexia, a syndrome of inflammatory-driven muscle wasting, AMPK activation could be beneficial. Here we show that the AMPK agonist AICAR suppresses IFNγ/TNFα-induced atrophy, while the mitochondrial inhibitor metformin does not. IFNγ/TNFα impair mitochondrial oxidative respiration in myotubes and promote a metabolic shift to aerobic glycolysis, similarly to metformin. In contrast, AICAR partially restored metabolic function. The effects of AICAR were prevented by the AMPK inhibitor Compound C and were reproduced with A-769662, a specific AMPK activator. AICAR and A-769662 co-treatment was found to be synergistic, suggesting that the anti-cachectic effects of these drugs are mediated through AMPK activation. AICAR spared muscle mass in mouse models of cancer and LPS induced atrophy. Together, our findings suggest a dual function for AMPK during inflammation-driven atrophy, wherein it can play a protective role when activated exogenously early in disease progression, but may contribute to anabolic suppression and atrophy when activated later through mitochondrial dysfunction and subsequent metabolic stress.


  • Hall, Derek T
  • Griss, Takla
  • Ma, Jennifer F
  • Sanchez, Brenda Janice
  • Sadek, Jason
  • Tremblay, Anne Marie K
  • Mubaid, Souad
  • Omer, Amr
  • Ford, Rebecca J
  • Bedard, Nathalie
  • Pause, Arnim
  • Wing, Simon S
  • Di Marco, Sergio
  • Steinberg, Gregory
  • Jones, Russell G
  • Gallouzi, Imed‐Eddine

publication date

  • July 2018

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