Manara - Qatar Research Repository
10 files

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

Version 2 2024-05-29, 09:18
Version 1 2024-05-29, 09:07
journal contribution
revised on 2024-05-29, 09:11 and posted on 2024-05-29, 09:18 authored by Derek T Hall, Takla Griss, Jennifer F Ma, Brenda Janice Sanchez, Jason Sadek, Anne Marie K Tremblay, Souad Mubaid, Amr Omer, Rebecca J Ford, Nathalie Bedard, Arnim Pause, Simon S Wing, Sergio Di Marco, Gregory R Steinberg, Russell G Jones, Imed‐Eddine Gallouzi

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.

Other Information

Published in: EMBO Molecular Medicine
See article on publisher's website:


Open Access funding provided by the Qatar National Library.

Qatar National Research Fund (NPRP8‐457‐3‐101), HuR-induced Cell Death of Breast Cancer Cells and Tumors: Molecular Mechanisms and Clinical Implication.



  • English


Springer Nature

Publication Year

  • 2018

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Science and Engineering - HBKU

Usage metrics

    College of Science and Engineering - HBKU



    Ref. manager