ArticleJCI insight2022
Altered branched-chain α-keto acid metabolism is a feature of NAFLD in individuals with severe obesity.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 42 citations in OpenAlex.
- Metabolic impact of dietary glycine supplementation in individuals with severe obesity.Scientific reports · 2025Trial
- The effects of low-fat dairy products fortified with 1500 IU vitamin DJournal of health, population, and nutrition · 2023Trial
- Associations of habitual coffee intake with testosterone and cardiometabolic markers: the Northern Finland birth cohort 1966 study.European journal of nutrition · 2026Article
- Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Metabolic markers of kidney function and oxidative stress are associated with heart failure with preserved ejection fraction (HFpEF) in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD).Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Hyperimonates A and B, a pair of unprecedented polyprenylated acylphloroglucinols fromActa pharmaceutica Sinica. B · 2026Article
- Rapamycin Reverses the Hepatic Response to Diet-Induced Metabolic Stress That Is Amplified by Aging.Aging cell · 2026Article
- Cytokeratin 18 fragment is associated with steatosis-associated fibrosis estimator score and lipid in patients with steatotic liver disease.World journal of hepatology · 2025Article
- Exploring the potential relationship between serum biomarkers in obese individuals and cancer using FTIR, metabolomics, and lipidomics.Metabolomics : Official journal of the Metabolomic Society · 2025Article
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
- Circulating BCKAs are closely associated with adipose tissue insulin resistance in type 2 diabetes.Diabetology & metabolic syndrome · 2025Article
- Short-term Physical Activity Reduces Metabolic-associated Steatohepatitis by Promoting the Degradation of Branched-chain Amino Acids in Skeletal Muscle.Journal of clinical and translational hepatology · 2025Article
- Metabolic Syndrome and Parkinson's Disease: Two Villains Join Forces.Brain sciences · 2025Article
- Research advances in branched-chain amino acid metabolism in tumors.Molecular and cellular biochemistry · 2025Review
- Circulating metabolite signatures indicate differential gut-liver crosstalk in lean and obese MASLD.JCI insight · 2025Article
- Integration of metabolomic and transcriptomic analyses reveals regulatory functions of the ChREBP transcription factor in energy metabolism.Cell reports · 2025Article
- Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Primary Roles of Branched Chain Amino Acids (BCAAs) and Their Metabolism in Physiology and Metabolic Disorders.Molecules (Basel, Switzerland) · 2024Review
- Integration of metabolomic and transcriptomic analyses reveals novel regulatory functions of the ChREBP transcription factor in energy metabolism.bioRxiv : the preprint server for biology · 2024Article
- Towards Metabolomic-Based Precision Approaches for Classifying and Treating Heart Failure.JACC. Basic to translational science · 2024Review
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
Hepatic de novo lipogenesis is influenced by the branched-chain α-keto acid dehydrogenase (BCKDH) kinase (BCKDK). Here, we aimed to determine whether circulating levels of the immediate substrates of BCKDH, the branched-chain α-keto acids (BCKAs), and hepatic BCKDK expression are associated with the presence and severity of nonalcoholic fatty liver disease (NAFLD). Eighty metabolites (3 BCKAs, 14 amino acids, 43 acylcarnitines, 20 ceramides) were quantified in plasma from 288 patients with bariatric surgery with severe obesity and scored liver biopsy samples. Metabolite principal component analysis factors, BCKAs, branched-chain amino acids (BCAAs), and the BCKA/BCAA ratio were tested for associations with steatosis grade and presence of nonalcoholic steatohepatitis (NASH). Of all analytes tested, only the Val-derived BCKA, α-keto-isovalerate, and the BCKA/BCAA ratio were associated with both steatosis grade and NASH. Gene expression analysis in liver samples from 2 independent bariatric surgery cohorts showed that hepatic BCKDK mRNA expression correlates with steatosis, ballooning, and levels of the lipogenic transcription factor SREBP1. Experiments in AML12 hepatocytes showed that SREBP1 inhibition lowered BCKDK mRNA expression. These findings demonstrate that higher plasma levels of BCKA and hepatic expression of BCKDK are features of human NAFLD/NASH and identify SREBP1 as a transcriptional regulator of BCKDK.
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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.