ArticleEMBO molecular medicine2018
The AMPK agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation-associated cachectic muscle wasting.
Article in EMBO molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Autophagy modulation in animal models of corneal diseases: a systematic review.Molecular and cellular biochemistry · 2020Pooled it
- The Secretome of a Cachexia-Inducing Lung Tumor Impairs Mitochondrial Function and Skeletal Muscle Differentiation.Cancers · 2026Article
- Parthenolide Attenuates Skeletal Muscle Atrophy Through Regulation of Protein Homeostasis and Inhibition of Inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The effects of tissue inflammation on cancer cachexia.Biochimica et biophysica acta. Molecular basis of disease · 2026Review
- Zinc Depletion Increases Susceptibility to AMPK-Induced Atrophic Responses in C2C12 Myotubes.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- Negative Impact of p21-Activated Kinase 4-Mediated AMP-Activated Protein Kinase Inhibition on Sarcopenia in Mice and Humans.MedComm · 2025Article
- Combating muscle atrophy: emerging therapeutic targets that are fiber-type-specific.The FEBS journal · 2025Review
- PRMT1 (protein arginine methyltransferase 1) is essential for neuromuscular junction and mitochondrial homeostasis via mitophagy regulation.Autophagy · 2025Article
- Hyperactivation of Transforming Growth Factor-β-Activated Kinase 1 Causes Skeletal Muscle Pathology Reminiscent of Inflammatory Myopathies.The American journal of pathology · 2025Article
- Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.Brain, behavior, & immunity - health · 2025Review
- Chronic treatment of old mice with AICAR reverses age-related changes in exercise performance and skeletal muscle gene expression.FASEB bioAdvances · 2025Article
- The Effect of Cachexia on the Feeding Regulation of Skeletal Muscle Protein Synthesis in Tumour-Bearing Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Research progress on AMPK in the pathogenesis and treatment of MASLD.Frontiers in immunology · 2025Review
- AMPK as a mediator of tissue preservation: time for a shift in dogma?Nature reviews. Endocrinology · 2024Review
- CCL2 signaling promotes skeletal muscle wasting in non-tumor and breast tumor models.Disease models & mechanisms · 2024Article
- Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer.Acta physiologica (Oxford, England) · 2024Article
- Administration of adiponectin receptor agonist AdipoRon relieves cancer cachexia by mitigating inflammation in tumour-bearing mice.Journal of cachexia, sarcopenia and muscle · 2024Article
- Immunoregulation in cancer-associated cachexia.Journal of advanced research · 2024Review
- Mitochondrial defects in sporadic inclusion body myositis-causes and consequences.Frontiers in cell and developmental biology · 2024Review
- The proteasome regulates body weight and systemic nutrient metabolism during fasting.American journal of physiology. Endocrinology and metabolism · 2023Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
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.
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