ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2021
Multiomics-Identified Intervention to Restore Ethanol-Induced Dysregulated Proteostasis and Secondary Sarcopenia in Alcoholic Liver Disease.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases.Hepatology (Baltimore, Md.) · 2021Guideline
- Trial
- Hyaluronan 35 prevents endotoxin-mediated dysregulated skeletal muscle proteostasis during ethanol exposure.American journal of physiology. Endocrinology and metabolism · 2026Article
- Alcohol-Mediated Skeletal Muscle Adaptations and Their Impact on Comorbidities.The American journal of pathology · 2026Review
- Voluntary Activity Wheel Running Improves Hyperammonaemia-Induced Skeletal Muscle Molecular and Metabolic Perturbations in Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Metabolic imprinting drives epithelial memory during mucosal fungal infection.bioRxiv : the preprint server for biology · 2025Article
- Integrated Multiomics Analyses of the Molecular Landscape of Sarcopenia in Alcohol-Related Liver Disease.Journal of cachexia, sarcopenia and muscle · 2025Article
- Investigation of Uncovering Molecular Mechanisms of Alcohol-Induced Female Infertility-A Rational Approach.Reproductive sciences (Thousand Oaks, Calif.) · 2024Review
- Alcohol Alters Skeletal Muscle Bioenergetic Function: A Scoping Review.International journal of molecular sciences · 2024Article
- Differential impact of sex on regulation of skeletal muscle mitochondrial function and protein homeostasis by hypoxia-inducible factor-1α in normoxia.The Journal of physiology · 2024Article
- Effects of chronic alcohol intoxication on aerobic exercise-induced adaptations in female mice.Journal of applied physiology (Bethesda, Md. : 1985) · 2024Article
- L-Isoleucine reverses hyperammonemia-induced myotube mitochondrial dysfunction and post-mitotic senescence.The Journal of nutritional biochemistry · 2024Article
- Binge drinking leads to an oxidative and metabolic imbalance in skeletal muscle during adolescence in rats: endocrine repercussion.Journal of physiology and biochemistry · 2023Article
- Dysregulated cellular redox status during hyperammonemia causes mitochondrial dysfunction and senescence by inhibiting sirtuin-mediated deacetylation.Aging cell · 2023Article
- Liver transplantation in the patient with physical frailty.Journal of hepatology · 2023Review
- Adaptive exhaustion during prolonged intermittent hypoxia causes dysregulated skeletal muscle protein homeostasis.The Journal of physiology · 2023Article
- Alcohol and Skeletal Muscle in Health and Disease.Alcohol research : current reviews · 2023Review
- Acute binge alcohol alters whole body metabolism and the time-dependent expression of skeletal muscle-specific metabolic markers for multiple days in mice.American journal of physiology. Endocrinology and metabolism · 2022Article
- Alcohol Induces Zebrafish Skeletal Muscle Atrophy through HMGB1/TLR4/NF-κB Signaling.Life (Basel, Switzerland) · 2022Article
- Side effects of amino acid supplements.Physiological research · 2022Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
BACKGROUND/
aimsSignaling and metabolic perturbations contribute to dysregulated skeletal muscle protein homeostasis and secondary sarcopenia in response to a number of cellular stressors including ethanol exposure. Using an innovative multiomics-based curating of unbiased data, we identified molecular and metabolic therapeutic targets and experimentally validated restoration of protein homeostasis in an ethanol-fed mouse model of liver disease.
methodsStudies were performed in ethanol-treated differentiated C2C12 myotubes and physiological relevance established in an ethanol-fed mouse model of alcohol-related liver disease (mALD) or pair-fed control C57BL/6 mice. Transcriptome and proteome from ethanol treated-myotubes and gastrocnemius muscle from mALD and pair-fed mice were analyzed to identify target pathways and molecules. Readouts including signaling responses and autophagy markers by immunoblots, mitochondrial oxidative function and free radical generation, and metabolic studies by gas chromatography-mass spectrometry and sarcopenic phenotype by imaging.
resultsMultiomics analyses showed that ethanol impaired skeletal muscle mTORC1 signaling, mitochondrial oxidative pathways, including intermediary metabolite regulatory genes, interleukin-6, and amino acid degradation pathways are β-hydroxymethyl-butyrate targets. Ethanol decreased mTORC1 signaling, increased autophagy flux, impaired mitochondrial oxidative function with decreased tricarboxylic acid cycle intermediary metabolites, ATP synthesis, protein synthesis and myotube diameter that were reversed by HMB. Consistently, skeletal muscle from mALD had decreased mTORC1 signaling, reduced fractional and total muscle protein synthesis rates, increased autophagy markers, lower intermediary metabolite concentrations, and lower muscle mass and fiber diameter that were reversed by β-hydroxymethyl-butyrate treatment.
conclusionAn innovative multiomics approach followed by experimental validation showed that β-hydroxymethyl-butyrate restores muscle protein homeostasis in liver disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.