ArticleOncotarget2017
Branched-chain amino acids prevent hepatic fibrosis and development of hepatocellular carcinoma in a non-alcoholic steatohepatitis mouse model.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- The Impact of the Alternate Mediterranean Diet (aMED) on the Prevention of Chronic Liver Disease: A Meta-Analysis of Observational Studies.Nutrients · 2025Pooled it
- Evaluation of the Therapeutic Potential ofNutrients · 2026Article
- Dietary intake and BCAA metabolism regulate pulmonary fibrosis through KDM4A-mediated epigenetic remodeling in male mice.Nature communications · 2026Article
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
- From bench to bedside: adipose tissue fibrosis in obesity, anti-diabetic therapies, and bariatric surgery.The Korean journal of internal medicine · 2026Review
- Evaluation methods of hepatic steatosis: From conventional techniques to emerging biomarkers.World journal of hepatology · 2026Review
- Metabolic characteristics in hepatocellular carcinoma: amino acid metabolic reprogramming.Molecular cancer · 2026Review
- Branched-chain amino acid transaminases as promising targets in tumor therapy.Frontiers in cell and developmental biology · 2026Review
- Article
- Article
- Chemoprevention of hepatocellular carcinoma.Hepatology communications · 2025Review
- Metabolic Adaptations in Cancer Progression: Optimization Strategies and Therapeutic Targets.Cancers · 2025Review
- Branched-chain amino acid and cancer: metabolism, immune microenvironment and therapeutic targets.Journal of translational medicine · 2025Review
- The association between dietary intake of branched-chain amino acids and the odds of nonalcoholic fatty liver disease among overweight and obese children and adolescents.Journal of diabetes and metabolic disorders · 2025Article
- Metabolic reprogramming in hepatocellular carcinoma: mechanisms and therapeutic implications.Experimental & molecular medicine · 2025Review
- Current and emerging strategies for the prevention of hepatocellular carcinoma.Nature reviews. Gastroenterology & hepatology · 2025Review
- Primary Roles of Branched Chain Amino Acids (BCAAs) and Their Metabolism in Physiology and Metabolic Disorders.Molecules (Basel, Switzerland) · 2024Review
- Branched-chain amino acids and their metabolites decrease human and rat hepatic stellate cell activation.Molecular biology reports · 2024Article
- Integrative proteogenomic profiling of high-risk prostate cancer samples from Chinese patients indicates metabolic vulnerabilities and diagnostic biomarkers.Nature cancer · 2024Article
- Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oral supplementation with branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in patients with liver cirrhosis potentially suppresses the incidence of hepatocellular carcinoma (HCC) and improves event-free survival. However, the detailed mechanisms of BCAA action have not been fully elucidated. BCAA were administered to atherogenic and high-fat (Ath+HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice. Liver histology, tumor incidence, and gene expression profiles were evaluated. Ath+HF diet mice developed hepatic tumors at a high frequency at 68 weeks. BCAA supplementation significantly improved hepatic steatosis, inflammation, fibrosis, and tumors in Ath+HF mice at 68 weeks. GeneChip analysis demonstrated the significant resolution of pro-fibrotic gene expression by BCAA supplementation. The anti-fibrotic effect of BCAA was confirmed further using platelet-derived growth factor C transgenic mice, which develop hepatic fibrosis and tumors. In vitro, BCAA restored the transforming growth factor (TGF)-β1-stimulated expression of pro-fibrotic genes in hepatic stellate cells (HSC). In hepatocytes, BCAA restored TGF-β1-induced apoptosis, lipogenesis, and Wnt/β-Catenin signaling, and inhibited the transformation of WB-F344 rat liver epithelial stem-like cells. BCAA repressed the promoter activity of TGFβ1R1 by inhibiting the expression of the transcription factor NFY and histone acetyltransferase p300. Interestingly, the inhibitory effect of BCAA on TGF-β1 signaling was mTORC1 activity-dependent, suggesting the presence of negative feedback regulation from mTORC1 to TGF-β1 signaling. Thus, BCAA induce an anti-fibrotic effect in HSC, prevent apoptosis in hepatocytes, and decrease the incidence of HCC; therefore, BCAA supplementation would be beneficial for patients with advanced liver fibrosis with a high risk of HCC.
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