ArticleNature metabolism2022
BCAA-BCKA axis regulates WAT browning through acetylation of PRDM16.
Article in Nature metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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54 citing papers in PubMed, 96 citations in OpenAlex.
- Article
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- The emerging role of branched-chain amino acid metabolism in obesity.International journal of obesity (2005) · 2026Review
- Metabolic reprogramming drives pancreatic β cell neogenesis from α cells.Nature chemical biology · 2026Article
- Association of BCAAs/BCKAs with pancreatic steatosis in patients with type 2 diabetes mellitus: A cross-sectional study.Journal of diabetes investigation · 2026Article
- Tumor-derived branched-chain α-keto acids activate Notch signaling in tumor-associated macrophages to limit immunity.Nature immunology · 2026Article
- Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dietary intake and BCAA metabolism regulate pulmonary fibrosis through KDM4A-mediated epigenetic remodeling in male mice.Nature communications · 2026Article
- CBP/p300 is critical for the expansion and maintenance of functional pancreatic α cell mass.Nature communications · 2026Article
- Leucine catabolic enzyme AUH regulates BAT thermogenesis via PPARγ HMGylation and RNA-binding function in male mice.Nature communications · 2026Article
- PTG-Dependent Glycogen Metabolic Dysfunction Drives Impaired Adipose Browning: A Novel Mechanism Linking PMAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identification and validation of the protective gene BCAT2 related to amino acid metabolism in idiopathic pulmonary fibrosis.Clinical and experimental medicine · 2026Article
- Nutritional Strategy to Minimize Early Lean Mass Loss after SG: The Role of Low-BCAA Soy Peptide Supplements.Obesity surgery · 2026Article
- Maternal gestational diabetes mellitus leads to adverse growth patterns and disease risk in offspring in vivo: evidence from cross-generational effects on gut microbiota.BMC microbiology · 2026Article
- Significance of neuroendocrine systems and the gut-brain axis (GBA) in the regulation of obesity.PeerJ · 2026Review
- Vascular Smooth Muscle Cell-Specific BCAT2 Deficiency Attenuates Diabetic Atherosclerotic Calcification via Histone Propionylation.Research (Washington, D.C.) · 2026Article
- From endocrine to immune: therapeutic potential of brown adipose tissue in remodelling the cardiovascular immune microenvironment.Frontiers in immunology · 2026Review
- Mitochondrial dysfunction in adipocyte differentiation: implications for obesity and metabolic syndrome intervention.Acta biochimica et biophysica Sinica · 2025Article
- Hepatocytic ankyrin repeat and SOCS box protein 3 deficiency alleviates metabolic dysfunction-associated steatotic liver disease by decreasing ubiquitin-mediated carnitine palmitoyl transferase 1A.Clinical and molecular hepatology · 2025Article
- Extract of Bombycis Feces suppressed 3T3-L1 adipogenesis resulting in the regulation of fatty acid-dependent energy consumption.Scientific reports · 2025Article
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12 authors at 5 institutions in 4 countries.
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Abstract
The link between branched-chain amino acids (BCAAs) and obesity has been known for decades but the functional role of BCAA metabolism in white adipose tissue (WAT) of obese individuals remains vague. Here, we show that mice with adipose tissue knockout of Bcat2, which converts BCAAs to branched-chain keto acids (BCKAs), are resistant to high-fat diet-induced obesity due to increased inguinal WAT browning and thermogenesis. Mechanistically, acetyl-CoA derived from BCKA suppresses WAT browning by acetylation of PR domain-containing protein 16 (PRDM16) at K915, disrupting the interaction between PRDM16 and peroxisome proliferator-activated receptor-γ (PPARγ) to maintain WAT characteristics. Depletion of BCKA-derived acetyl-CoA robustly prompts WAT browning and energy expenditure. In contrast, BCKA supplementation re-establishes high-fat diet-induced obesity in Bcat2 knockout mice. Moreover, telmisartan, an anti-hypertension drug, significantly represses Bcat2 activity via direct binding, resulting in enhanced WAT browning and reduced adiposity. Strikingly, BCKA supplementation reverses the lean phenotype conferred by telmisartan. Thus, we uncover the critical role of the BCAA-BCKA axis in WAT browning.
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