Trial reportAmerican journal of physiology. Endocrinology and metabolism2015
Cross-talk between branched-chain amino acids and hepatic mitochondria is compromised in nonalcoholic fatty liver disease.
Trial report in American journal of physiology. Endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 108 citations in OpenAlex.
- Angel or demon? The dual role of branched-chain amino acids in chronic inflammatory and injury-related diseases.Frontiers in immunology · 2026Review
- Metabolic Phenotypes, Genotypes, and Gut Microbiome Signatures in Obesity: Implications for Precision Nutrition Strategies in Type 2 Diabetes Prevention.Nutrition reviews · 2026Review
- The association between dietary consumption of amino acids and the risk of non-alcoholic fatty liver disease: a case-control study.Nutrition & metabolism · 2025Article
- Targeted metabolomics reveals bioactive inflammatory mediators from gut into blood circulation in children with NAFLD.NPJ biofilms and microbiomes · 2025Article
- Metabolomics in cardiometabolic diseases: Key biomarkers and therapeutic implications for insulin resistance and diabetes.Journal of internal medicine · 2025Review
- A Comprehensive Pilot Study to Elucidate the Distinct Gut Microbial Composition and Its Functional Significance in Cardio-Metabolic Disease.Biochemical genetics · 2025Article
- 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
- Hyperinsulinemic male LEW.1WR1 rats show early signs of impaired liver metabolism.Experimental and molecular pathology · 2025Article
- NAD metabolic therapy in metabolic dysfunction-associated steatotic liver disease: Possible roles of gut microbiota.iScience · 2024Review
- Role of Insulin Resistance in the Development of Nonalcoholic Fatty Liver Disease in People With Type 2 Diabetes: From Bench to Patient Care.Diabetes spectrum : a publication of the American Diabetes Association · 2024Article
- Metabolomic Insights into the Mechanisms of Ganoderic Acid: Protection against α-Amanitin-Induced Liver Injury.Metabolites · 2023Article
- Article
- Mitochondrial Dysfunction-Associated Mechanisms in the Development of Chronic Liver Diseases.Biology · 2023Review
- Thioredoxin/Glutaredoxin Systems and Gut Microbiota in NAFLD: Interplay, Mechanism, and Therapeutical Potential.Antioxidants (Basel, Switzerland) · 2023Review
- Cell-autonomous effect of cardiomyocyte branched-chain amino acid catabolism in heart failure in mice.Acta pharmacologica Sinica · 2023Article
- Branched-Chain Amino Acids in Computed Tomography-Defined Adipose Depots and Coronary Artery Disease: A PROMISE Trial Biomarker Substudy.Journal of the American Heart Association · 2023Article
- An early prediction model for gestational diabetes mellitus based on metabolomic biomarkers.Diabetology & metabolic syndrome · 2023Article
- Branched-chain amino acids alter cellular redox to induce lipid oxidation and reduce de novo lipogenesis in the liver.American journal of physiology. Endocrinology and metabolism · 2023Article
- Electroacupuncture treatment ameliorates metabolic disorders in obese ZDF rats by regulating liver energy metabolism and gut microbiota.Frontiers in endocrinology · 2023Article
- The association between dietary amino acids and the risk of nonalcoholic fatty liver disease among Tehranian adults: a case-control study.BMC nutrition · 2022Article
6 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
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Elevated plasma branched-chain amino acids (BCAA) in the setting of insulin resistance have been relevant in predicting type 2 diabetes mellitus (T2DM) onset, but their role in the etiology of hepatic insulin resistance remains uncertain. We determined the link between BCAA and dysfunctional hepatic tricarboxylic acid (TCA) cycle, which is a central feature of hepatic insulin resistance and nonalcoholic fatty liver disease (NAFLD). Plasma metabolites under basal fasting and euglycemic hyperinsulinemic clamps (insulin stimulation) were measured in 94 human subjects with varying degrees of insulin sensitivity to identify their relationships with insulin resistance. Furthermore, the impact of elevated BCAA on hepatic TCA cycle was determined in a diet-induced mouse model of NAFLD, utilizing targeted metabolomics and nuclear magnetic resonance (NMR)-based metabolic flux analysis. Insulin stimulation revealed robust relationships between human plasma BCAA and indices of insulin resistance, indicating chronic metabolic overload from BCAA. Human plasma BCAA and long-chain acylcarnitines also showed a positive correlation, suggesting modulation of mitochondrial metabolism by BCAA. Concurrently, mice with NAFLD failed to optimally induce hepatic mTORC1, plasma ketones, and hepatic long-chain acylcarnitines, following acute elevation of plasma BCAA. Furthermore, elevated BCAA failed to induce multiple fluxes through hepatic TCA cycle in mice with NAFLD. Our data suggest that BCAA are essential to mediate efficient channeling of carbon substrates for oxidation through mitochondrial TCA cycle. Impairment of BCAA-mediated upregulation of the TCA cycle could be a significant contributor to mitochondrial dysfunction in NAFLD.
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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.