ArticleCell metabolism2018
The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase.
Article in Cell metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 224 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
224 citing papers in PubMed, 2 syntheses or guidelines pooled it, 340 citations in OpenAlex.
- Metabolomic biomarkers and metabolic remodelling in genetically characterised hypertrophic cardiomyopathy: a systematic review.Metabolomics : Official journal of the Metabolomic Society · 2026Pooled it
- Pooled it
- A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes.Nature communications · 2022Trial
- RkMsn4, a zinc finger transcription factor, regulates carotenoid and lipid metabolism to enhance tolerance to environmental stress inApplied and environmental microbiology · 2026Article
- Effects of DietaryAnimals : an open access journal from MDPI · 2026Article
- Manganese availability determines insulin sensitivity by enhancing Akt activity.bioRxiv : the preprint server for biology · 2026Article
- BCKDK protects against obesity-induced cardiac remodelling and dysfunction by alleviating mitochondrial oxidative stress and ROS-driven MAPK signalling.Redox biology · 2026Article
- Loss of TAFAZZIN leads to perturbation of amino acid metabolism and reduction of collagen synthesis.bioRxiv : the preprint server for biology · 2026Article
- Branched chain amino acid metabolism and microbiome in adolescents with obesity during weight loss therapy.The Journal of clinical investigation · 2026Observational
- Suppression of UCP2 alleviates leukemogenesis by enhancing branched-chain amino acids-induced oxidative stress via activating the PI3K/AKT/mTOR signaling pathway.Genes & diseases · 2026Article
- Association between Body Fat composition and serum branched chain amino acids in patients with visceral obesity.BMC endocrine disorders · 2026Article
- A metabolic basis for motor deficits in mice lacking BCKDK.The Journal of nutritional biochemistry · 2026Article
- De Novo Lipogenesis in Clear Cell Renal Cell Carcinoma: Mechanistic Insights and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Plasma metabolites after 10-weeks of glucose vs fructose-sweetened beverages in subjects with overweight/obesity.Journal of the Endocrine Society · 2026Article
- Glutamine-driven reductive TCA cycle metabolism supports aged muscle stem cell function via de novo lipogenesis.Nature aging · 2026Article
- Loss of Propionyl-CoA Carboxylase Reprograms Hepatic Metabolism by Suppressing Mitochondrial Pyruvate Carboxylation and Fatty Acid Oxidation.bioRxiv : the preprint server for biology · 2026Article
- Branched-chain α-keto acids impair glucose-stimulated insulin secretion in pancreatic β-cells under diabetes by reactivating the LDHA-lactate axis.Nature communications · 2026Article
- Gut microbiota-derived L-theanine promotes host branched-chain amino acid catabolism.Nature microbiology · 2026Article
- Metabolic characteristics in hepatocellular carcinoma: amino acid metabolic reprogramming.Molecular cancer · 2026Review
- Angel or demon? The dual role of branched-chain amino acids in chronic inflammatory and injury-related diseases.Frontiers in immunology · 2026Review
164 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
21 authors at 4 institutions in 1 country.
Funding
Abstract
Branched-chain amino acids (BCAA) are strongly associated with dysregulated glucose and lipid metabolism, but the underlying mechanisms are poorly understood. We report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that regulates branched-chain ketoacid dehydrogenase (BCKDH), the committed step of BCAA catabolism, lowers circulating BCAA, reduces hepatic steatosis, and improves glucose tolerance in the absence of weight loss in Zucker fatty rats. Phosphoproteomics analysis identified ATP-citrate lyase (ACL) as an alternate substrate of BDK and PPM1K. Hepatic overexpression of BDK increased ACL phosphorylation and activated de novo lipogenesis. BDK and PPM1K transcript levels were increased and repressed, respectively, in response to fructose feeding or expression of the ChREBP-β transcription factor. These studies identify BDK and PPM1K as a ChREBP-regulated node that integrates BCAA and lipid metabolism. Moreover, manipulation of the BDK:PPM1K ratio relieves key metabolic disease phenotypes in a genetic model of severe obesity.
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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.