ArticleNutrition & diabetes2022
Detrimental effects of branched-chain amino acids in glucose tolerance can be attributed to valine induced glucotoxicity in skeletal muscle.
Article in Nutrition & diabetes, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Gut-associated metabolites and diabetes pathology: a systematic review.Frontiers in endocrinology · 2025Pooled it
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.Nature aging · 2026Article
- Decoding the Gut-Fat-Heart Axis: From Molecular Communication Networks to Clinical Translation Strategies.International journal of molecular sciences · 2026Review
- Exploring exosome-related genes as candidate biomarkers in primary immune thrombocytopenia through transcriptomics and preliminary experimental validation.Scientific reports · 2026Article
- Expression and clinical significance of fatty acid metabolism-related genes in PBMCs of SSc patients.Clinical rheumatology · 2026Article
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.bioRxiv : the preprint server for biology · 2025Article
- Branched-chain amino acids alleviate NAFLD via inhibiting de novo lipogenesis and activating fatty acid β-oxidation in laying hens.Redox biology · 2024Article
- Effect of mTORC Agonism via MHY1485 with and without Rapamycin on C2C12 Myotube Metabolism.International journal of molecular sciences · 2024Article
- Article
- Valine induces inflammation and enhanced adipogenesis in lean mice by multi-omics analysis.Frontiers in nutrition · 2024Article
- Valine metabolite, 3-hydroxyisobutyrate, promotes lipid metabolism and cell proliferation in porcine mammary gland epithelial cells.Frontiers in nutrition · 2024Article
- Branched chain amino acids harbor distinct and often opposing effects on health and disease.Communications medicine · 2023Article
- Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice.Cell metabolism · 2023Article
- Article
- Cell-autonomous effect of cardiomyocyte branched-chain amino acid catabolism in heart failure in mice.Acta pharmacologica Sinica · 2023Article
- The Selective LAT1 Inhibitor JPH203 Enhances Mitochondrial Metabolism and Content in Insulin-Sensitive and Insulin-Resistant C2C12 Myotubes.Metabolites · 2023Article
- Review
- Heptadecanoic Acid Is Not a Key Mediator in the Prevention of Diet-Induced Hepatic Steatosis and Insulin Resistance in Mice.Nutrients · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveCurrent data regarding the roles of branched-chain amino acids (BCAA) in metabolic health are rather conflicting, as positive and negative effects have been attributed to their intake.
methodsTo address this, individual effects of leucine and valine were elucidated in vivo (C57BL/6JRj mice) with a detailed phenotyping of these supplementations in high-fat (HF) diets and further characterization with in vitro approaches (C2C12 myocytes).
resultsHere, we demonstrate that under HF conditions, leucine mediates beneficial effects on adiposity and insulin sensitivity, in part due to increasing energy expenditure-likely contributing partially to the beneficial effects of a higher milk protein intake. On the other hand, valine feeding leads to a worsening of HF-induced health impairments, specifically reducing glucose tolerance/insulin sensitivity. These negative effects are driven by an accumulation of the valine-derived metabolite 3-hydroxyisobutyrate (3-HIB). Higher plasma 3-HIB levels increase basal skeletal muscle glucose uptake which drives glucotoxicity and impairs myocyte insulin signaling.
conclusionThese data demonstrate the detrimental role of valine in an HF context and elucidate additional targetable pathways in the etiology of BCAA-induced obesity and insulin resistance.
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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.