ArticleJournal of cachexia, sarcopenia and muscle2025
Voluntary Activity Wheel Running Improves Hyperammonaemia-Induced Skeletal Muscle Molecular and Metabolic Perturbations in Mice.
Article in Journal of cachexia, sarcopenia and muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Hypoxia-inducible factor-1a (HIF1a) as a context-dependent integrator of metabolic stress in skeletal muscle.The Journal of physiology · 2026Review
- Voluntary wheel running modulates murine gut microbiome during hyperammonemic stress.Microbiology spectrum · 2026Article
- Hyaluronan 35 prevents endotoxin-mediated dysregulated skeletal muscle proteostasis during ethanol exposure.American journal of physiology. Endocrinology and metabolism · 2026Article
- Voluntary Activity Wheel Running Improves Hyperammonaemia-Induced Skeletal Muscle Molecular and Metabolic Perturbations in Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
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Authors and funding
14 authors.
Funding
Abstract
aimVoluntary exercise improves clinical outcomes in healthy subjects, but increased muscle ammoniagenesis may limit beneficial responses during hyperammonaemia in chronic diseases. Responses to 4-weeks voluntary wheel running (VWR) were compared with usual activity (UA) to determine if hyperammonaemia alters VWR responses and if VWR alters muscle responses to hyperammonaemia.
methodsEight- to 10-week-old male C57BL/6J mice were treated with 6 weeks of subcutaneous infusion of 2.5 mmol kg
resultsGastrocnemius muscle mass (p < 0.01), muscle fibre area (p < 0.01), and grip strength were lower in AmAc-UA than in PBS-UA mice and higher with VWR than UA in AmAc mice (p < 0.001). Expression of electron transport chain proteins and some components of mitochondrial oxidative function were less (p < 0.05 or less) in AmAc-UA than PBS-UA, and these perturbations were reversed in the AmAc-VWR mice (p < 0.05 or less). Global muscle protein synthesis (p < 0.05) and components of the mTORC1 pathway expression (p < 0.05) were higher, while myostatin expression was lower with VWR than UA in AmAc mice (p < 0.05). Expression of autophagy markers P62 and LC3-II was not different with VWR or UA in AmAc mice, while Beclin1 was higher in VWR compared with UA, regardless of treatment group (p < 0.001). Expression of muscle ammonia disposal pathway enzymes, including glutamate dehydrogenase and pyrroline-5-carboxylate synthase, was higher (p ≤ 0.05) in AmAc-UA versus PBS-UA and increased in only PBS-VWR mice (p < 0.05).
conclusionVWR reverses hyperammonaemia-induced sarcopenia, protein synthesis/autophagy signalling perturbations, and mitochondrial oxidative dysfunction. Muscle mass, grip strength, signalling, and mitochondrial responses to VWR were not affected by hyperammonaemia. Increased expression of enzymes involved in the ammonia disposal pathway in skeletal muscle may be an adaptive response to hyperammonaemia. These data provide the rationale for exercise programmes in chronic diseases, including cirrhosis, even with hyperammonaemia.
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