气候变化领域集成服务门户(CCPortal): Butyrate enhances CPT1A activity to promote fatty acid oxidation and iTreg differentiation

CCPortal

DOI	10.1073/pnas.2014681118
	Butyrate enhances CPT1A activity to promote fatty acid oxidation and iTreg differentiation
	Hao F.; Tian M.; Zhang X.; Jin X.; Jiang Y.; Sun X.; Wang Y.; Peng P.; Liu J.; Xia C.; Feng Y.; Wei M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:22
英文摘要	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 shortchain 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 andmitigation 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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Butyrate; CPT1A; Fatty acid oxidation; Inflammatory bowel disease; ITreg
语种	英语
scopus关键词	acetate coenzyme A ligase; butyric acid; carnitine palmitoyltransferase I; CD4 antigen; interleukin 2 receptor alpha; long chain fatty acid coenzyme A ligase; malonyl coenzyme A; transcription factor FOXP3; acetate coenzyme A ligase; ACSS2 protein, mouse; butyric acid derivative; carnitine palmitoyltransferase; CPT1B protein, mouse; fatty acid; animal cell; animal experiment; animal model; animal tissue; Article; CD4+ T lymphocyte; colitis; controlled study; dendritic cell; enzyme activity; fatty acid oxidation; female; flow cytometry; homeostasis; lymphocyte differentiation; mouse; nonhuman; protein expression; regulatory T lymphocyte; upregulation; animal; cell differentiation; gene expression regulation; immunology; intestine flora; oxidation reduction reaction; regulatory T lymphocyte; Acetate-CoA Ligase; Animals; Butyrates; Carnitine O-Palmitoyltransferase; Cell Differentiation; Fatty Acids; Gastrointestinal Microbiome; Gene Expression Regulation, Enzymologic; Mice; Oxidation-Reduction; T-Lymphocytes, Regulatory; Up-Regulation
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251166
作者单位	Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, 130024, China
推荐引用方式 GB/T 7714	Hao F.,Tian M.,Zhang X.,et al. Butyrate enhances CPT1A activity to promote fatty acid oxidation and iTreg differentiation[J],2021,118(22).
APA	Hao F..,Tian M..,Zhang X..,Jin X..,Jiang Y..,...&Wei M..(2021).Butyrate enhances CPT1A activity to promote fatty acid oxidation and iTreg differentiation.Proceedings of the National Academy of Sciences of the United States of America,118(22).
MLA	Hao F.,et al."Butyrate enhances CPT1A activity to promote fatty acid oxidation and iTreg differentiation".Proceedings of the National Academy of Sciences of the United States of America 118.22(2021).