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10.15252/emmm.201708307

http://scihub22266oqcxt.onion/10.15252/emmm.201708307
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C6034131!6034131!29844217
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suck abstract from ncbi


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pmid29844217      EMBO+Mol+Med 2018 ; 10 (7): ä
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  • The AMPK agonist 5?aminoimidazole?4?carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation?associated cachectic muscle wasting #MMPMID29844217
  • Hall DT; Griss T; Ma JF; Sanchez BJ; Sadek J; Tremblay AMK; Mubaid S; Omer A; Ford RJ; Bedard N; Pause A; Wing SS; Di Marco S; Steinberg GR; Jones RG; Gallouzi I
  • EMBO Mol Med 2018[Jul]; 10 (7): ä PMID29844217show ga
  • 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 IFN?/TNF??induced atrophy, while the mitochondrial inhibitor metformin does not. IFN?/TNF? 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.
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