ArticleCell reports2023
Branched-chain keto acids inhibit mitochondrial pyruvate carrier and suppress gluconeogenesis in hepatocytes.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Nardilysin regulatesBiochemistry and biophysics reports · 2026Article
- The emerging role of branched-chain amino acid metabolism in obesity.International journal of obesity (2005) · 2026Review
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- Branching out takes anti-tumor immunity down a NOTCH.Nature immunology · 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
- Branched-chain amino acid metabolism and macrophage polarization: potential regulatory nodes and therapeutic targets in diabetes-associated metabolic inflammation.Frontiers in cellular and infection microbiology · 2026Review
- Impact of keto leucine and isoleucine on CHO cell central carbon metabolism and performance in fed-batch and steady-state perfusion.Frontiers in bioengineering and biotechnology · 2026Article
- Branched-chain amino acids in muscle growth: mechanisms, physiological functions, and applications.Journal of animal science and biotechnology · 2025Review
- BCKDK accelerates the progression of diabetic kidney disease by regulating leucine-mediated metabolic remodelling in renal tubular cells.Diabetologia · 2025Article
- Adenine base editing rescues disrupted BCKDH function and reduces BCAAs toxic accumulation in maple syrup urine disease patient iPSC-hepatic organoids.Stem cell research & therapy · 2025Article
- Emerging Insights into the Relationship Between Amino Acid Metabolism and Diabetic Cardiomyopathy.Biomolecules · 2025Review
- Liver Transplantation and Metabolic Dysfunction Associated Steatotic Liver Disease Is Associated with Markers of Metabolic Risk and Inflammation.Digestive diseases and sciences · 2025Article
- Phosphatase activity-based PPM1K: a key player in the regulation of mitochondrial function and its multifaceted impact in diseases.Molecular and cellular biochemistry · 2025Review
- Impaired cardiac branched-chain amino acid metabolism in a novel model of diabetic cardiomyopathy.Cardiovascular diabetology · 2025Article
- BCAA catabolism targeted therapy for heart failure with preserved ejection fraction.Theranostics · 2025Article
- Circulating branched-chain amino acids and the risk of major adverse cardiovascular events in the UK biobank.Frontiers in endocrinology · 2025Article
- Primary Roles of Branched Chain Amino Acids (BCAAs) and Their Metabolism in Physiology and Metabolic Disorders.Molecules (Basel, Switzerland) · 2024Review
- Brown Fat and Metabolic Health: The Diverse Functions of Dietary Components.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- BCKDH kinase promotes hepatic gluconeogenesis independent of BCKDHA.Cell death & disease · 2024Article
- Glucose-1,6-bisphosphate: A new gatekeeper of cerebral mitochondrial pyruvate uptake.Molecular metabolism · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Branched-chain amino acid (BCAA) metabolism is linked to glucose homeostasis, but the underlying signaling mechanisms are unclear. We find that gluconeogenesis is reduced in mice deficient of Ppm1k, a positive regulator of BCAA catabolism, which protects against obesity-induced glucose intolerance. Accumulation of branched-chain keto acids (BCKAs) inhibits glucose production in hepatocytes. BCKAs suppress liver mitochondrial pyruvate carrier (MPC) activity and pyruvate-supported respiration. Pyruvate-supported gluconeogenesis is selectively suppressed in Ppm1k-deficient mice and can be restored with pharmacological activation of BCKA catabolism by BT2. Finally, hepatocytes lack branched-chain aminotransferase that alleviates BCKA accumulation via reversible conversion between BCAAs and BCKAs. This renders liver MPC most susceptible to circulating BCKA levels hence a sensor of BCAA catabolism.
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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.