ArticleProceedings of the National Academy of Sciences of the United States of America2021
Butyrate enhances CPT1A activity to promote fatty acid oxidation and iTreg differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- Short-chain fatty acids and type 2 diabetes: a bibliometric analysis of knowledge structure, research hotspots, and future directions.Frontiers in microbiology · 2025Pooled it
- Maternal Diglyceride Diet Attenuates Selected Metabolic Effects of Maternal High-Fat Feeding in Offspring via Energy Metabolism and Microbiota Modulation.Food science & nutrition · 2026Article
- FTSJ3-Mediated 2'-O-Methylation of HSPA5 mRNA Stabilizes BOP1 via SUMOylation to Drive DRP1-Dependent Mitochondrial Fission and Fatty Acid Oxidation in Lung Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanical stretch promotes osteogenesis in the midpalatal suture by enhancing neutrophil fatty acid oxidation through the S1PR1/STAT3 axis.Mechanobiology in medicine · 2026Article
- Hepatocyte RAP1A Deletion Impairs Lipid Catabolism and Worsens Steatosis via Autophagy Activation.Diabetes & metabolism journal · 2026Article
- CPT1A through succinylation regulates the CTCF/LINC01503‒91aa feedback loop to promote gemcitabine resistance in pancreatic ductal adenocarcinoma.Clinical and translational medicine · 2026Article
- Current evidence and emerging therapeutic strategies for non-exercise interventions in sarcopenia associated with chronic obstructive pulmonary disease: a narrative review.Journal of thoracic disease · 2026Review
- Oral probiotic delivery-based therapeutic strategies for inflammatory bowel disease.Asian journal of pharmaceutical sciences · 2026Review
- ACSS2-KAT5 complex-driven histone crotonylation orchestrates a pro-inflammatory program to promote the transition from MASLD to MASH.Nature communications · 2026Article
- Microbiota-Derived Metabolites in the Epigenetic Regulation of Redox Homeostasis.Antioxidants (Basel, Switzerland) · 2026Review
- The Microbiota Metabolite-Joint Axis: Mechanistic Insights and Therapeutic Targets for Osteoarthritis.Biomedicines · 2026Review
- Activation of PPARγ and CPT1A Mediates the Hepatoprotective Effect of Ginsenoside CK against NAFLD in Rats.Biological procedures online · 2026Article
- Microbiota-derived metabolites and cardiovascular implications in Inflammatory Bowel Disease (IBD).Molecular medicine (Cambridge, Mass.) · 2026Review
- Review
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- Roseburia intestinalis ameliorates adolescent depression via GPR43‑dependent Treg cell expansion and suppression of neuroinflammation.Journal of neuroinflammation · 2026Article
- Bacteroides coprocola protects dopaminergic neurons in rotenone-induced Parkinson's disease mouse model by modulating gut microbiota dysbiosis and inhibiting the NLRP3 signaling pathway.Translational neurodegeneration · 2026Article
- Obesity is the culprit behind fatty acid-induced inflammation.Nutrition & metabolism · 2026Review
- Dysfunction of mitochondria in intestinal epithelial cells: a key player in the pathogenesis of inflammatory bowel diseases.Gastroenterology report · 2026Review
- Mucosa-associated bacteria and metabolites in inflammatory bowel disease: from inside to insight.NPJ biofilms and microbiomes · 2026Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inducible regulatory T (iTreg) cells play a crucial role in immune suppression and are important for the maintenance of immune homeostasis. Mounting evidence has demonstrated connections between iTreg differentiation and metabolic reprogramming, especially rewiring in fatty acid oxidation (FAO). Previous work showed that butyrate, a specific type of short-chain fatty acid (SCFA) readily produced from fiber-rich diets through microbial fermentation, was critical for the maintenance of intestinal homeostasis and capable of promoting iTreg generation by up-regulating histone acetylation for gene expression as an HDAC inhibitor. Here, we revealed that butyrate could also accelerate FAO to facilitate iTreg differentiation. Moreover, butyrate was converted, by acyl-CoA synthetase short-chain family member 2 (ACSS2), into butyryl-CoA (BCoA), which up-regulated CPT1A activity through antagonizing the association of malonyl-CoA (MCoA), the best known metabolic intermediate inhibiting CPT1A, to promote FAO and thereby iTreg differentiation. Mutation of CPT1A at Arg243, a reported amino acid required for MCoA association, impaired both MCoA and BCoA binding, indicating that Arg243 is probably the responsible site for MCoA and BCoA association. Furthermore, blocking BCoA formation by ACSS2 inhibitor compromised butyrate-mediated iTreg generation and mitigation of mouse colitis. Together, we unveil a previously unappreciated role for butyrate in iTreg differentiation and illustrate butyrate-BCoA-CPT1A axis for the regulation of immune homeostasis.
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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.