ArticleCell reports2021
SIRT4 is an early regulator of branched-chain amino acid catabolism that promotes adipogenesis.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 65 citations in OpenAlex.
- Review
- Dietary intake and BCAA metabolism regulate pulmonary fibrosis through KDM4A-mediated epigenetic remodeling in male mice.Nature communications · 2026Article
- SIRT4 regulates antiviral and autoimmune responses by promoting cGAS-mediated signaling pathways.EMBO reports · 2026Article
- The role of SIRT4 in obesity: from molecular mechanisms to clinical implications.International journal of obesity (2005) · 2026Review
- Integrative bioinformatics and machine learning approach unveils potential biomarkers linking coronary atherosclerosis and glutamine metabolism-associated gene.Journal of cardiothoracic surgery · 2025Article
- Regulation of adipogenesis by nucleotides.Biochemical Society transactions · 2025Review
- SIRT4 Controls Macrophage Function and Wound Healing through Control of Protein Itaconylation in Mice.bioRxiv : the preprint server for biology · 2025Article
- Mitochondrial substrate oxidation regulates distinct cell differentiation outcomes.Trends in cell biology · 2025Article
- Deciphering the anti-obesity mechanisms of pharmabiotic probiotics through advanced multiomics analysis.iScience · 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
- SIRT4 Controls Acetyl-CoA Synthesis to Promote Stemness and Invasiveness of Hepatocellular Carcinoma through Deacetylating MCCC2.International journal of biological sciences · 2025Article
- Recent advances in gut microbiota-mediated regulation of fat deposition and metabolic disorders.Microbiome research reports · 2025Review
- Crosstalk between adipogenesis and aging: role of polyphenols in combating adipogenic-associated aging.Immunity & ageing : I & A · 2024Review
- BCAA was more closely associated with visceral fat area than subcutaneous fat area in patients of type 2 diabetes mellitus: a cross-sectional study.BMC endocrine disorders · 2024Article
- Interplay Between the Circadian Clock and Sirtuins.International journal of molecular sciences · 2024Review
- Disruption of nucleotide biosynthesis reprograms mitochondrial metabolism to inhibit adipogenesis.Journal of lipid research · 2024Article
- Article
- Host-microbe interactions rewire metabolism in a C. elegans model of leucine breakdown deficiency.Nature metabolism · 2024Article
- A High-Fat and High-Fructose Diet Exacerbates Liver Dysfunction by Regulating Sirtuins in a Murine Model.Life (Basel, Switzerland) · 2024Article
- SIRT4 loss reprograms intestinal nucleotide metabolism to support proliferation following perturbation of homeostasis.Cell reports · 2024Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Upon nutrient stimulation, pre-adipocytes undergo differentiation to transform into mature adipocytes capable of storing nutrients as fat. We profiled cellular metabolite consumption to identify early metabolic drivers of adipocyte differentiation. We find that adipocyte differentiation raises the uptake and consumption of numerous amino acids. In particular, branched-chain amino acid (BCAA) catabolism precedes and promotes peroxisome proliferator-activated receptor gamma (PPARγ), a key regulator of adipogenesis. In early adipogenesis, the mitochondrial sirtuin SIRT4 elevates BCAA catabolism through the activation of methylcrotonyl-coenzyme A (CoA) carboxylase (MCCC). MCCC supports leucine oxidation by catalyzing the carboxylation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA. Sirtuin 4 (SIRT4) expression is decreased in adipose tissue of numerous diabetic mouse models, and its expression is most correlated with BCAA enzymes, suggesting a potential role for SIRT4 in adipose pathology through the alteration of BCAA metabolism. In summary, this work provides a temporal analysis of adipocyte differentiation and uncovers early metabolic events that stimulate transcriptional reprogramming.
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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.