BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21

doi:10.1186/s40168-024-01872-3

科研成果详情

题名	BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21
作者	Zheng, Hong1; Zhang, Xi 1; Li, Chen 1; Wang, Die 1; Shen, Yuying1; Lu, Jiahui1; Zhao, Liangcai1; Li, Xiaokun1,2; Gao, Hongchang1,2
发表日期	2024-08-24
发表期刊	Microbiome 影响因子和分区
语种	英语
原始文献类型	Article
关键词	BCAA Diabetes Fibrosis Mitochondria Gut microbiota Heart
其他关键词	CHAIN AMINO-ACIDS ; TRIMETHYLAMINE-N-OXIDE ; FACTOR 21 PROTECTS ; GUT MICROBIOTA ; PPAR-ALPHA ; METABOLISM ; EXPRESSION ; MECHANISMS ; DISEASE ; HEALTH
摘要	BackgroundDiabetic cardiomyopathy (DCM) is one of leading causes of diabetes-associated mortality. The gut microbiota-derived branched-chain amino acids (BCAA) have been reported to play a central role in the onset and progression of DCM, but the potential mechanisms remain elusive.ResultsWe found the type 1 diabetes (T1D) mice had higher circulating BCAA levels due to a reduced BCAA degradation ability of the gut microbiota. Excess BCAA decreased hepatic FGF21 production by inhibiting PPAR alpha signaling pathway and thereby resulted in a higher expression level of cardiac LAT1 via transcription factor Zbtb7c. High cardiac LAT1 increased the levels of BCAA in the heart and then caused mitochondrial damage and myocardial apoptosis through mTOR signaling pathway, leading to cardiac fibrosis and dysfunction in T1D mice. Additionally, transplant of faecal microbiota from healthy mice alleviated cardiac dysfunction in T1D mice, but this effect was abolished by FGF21 knockdown.ConclusionsOur study sheds light on BCAA-mediated crosstalk among the gut microbiota, liver and heart to promote DCM and FGF21 serves as a key mediator.BVPaWWrrqVUsPwxN3tcRV1Video AbstractConclusionsOur study sheds light on BCAA-mediated crosstalk among the gut microbiota, liver and heart to promote DCM and FGF21 serves as a key mediator.BVPaWWrrqVUsPwxN3tcRV1Video Abstract
资助项目	National Natural Science Foundation of China; Laboratory Animal Center of Wenzhou Medical University for Technical Services
出版者	BMC
ISSN	2049-2618
卷号	12 期号:1
DOI	10.1186/s40168-024-01872-3
页数	23
WOS类目	Microbiology
WOS研究方向	Microbiology
WOS记录号	WOS:001297026300002
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39182099
SCOPUSEID	2-s2.0-85202267141
通讯作者地址	[Gao, Hongchang]Wenzhou Med Univ, Sch Pharmaceut Sci, Oujiang Lab, Wenzhou 325035, Peoples R China. ; [Gao, Hongchang]Wenzhou Med Univ, Inst Aging, Key Lab Alzheimers Dis Zhejiang Prov, Wenzhou 325035, Peoples R China.
Scopus学科分类	Microbiology;Microbiology (medical)
SCOPUS_ID	SCOPUS_ID:85202267141
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/217476
专题	药学院（分析测试中心）卓越中心_老年研究院
通讯作者	Gao, Hongchang
作者单位	1.Wenzhou Med Univ, Sch Pharmaceut Sci, Oujiang Lab, Wenzhou 325035, Peoples R China; 2.Wenzhou Med Univ, Inst Aging, Key Lab Alzheimers Dis Zhejiang Prov, Wenzhou 325035, Peoples R China
第一作者单位	药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）; 温州医科大学
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Zheng, Hong,Zhang, Xi,Li, Chen,et al. BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21[J]. Microbiome,2024,12(1).
APA	Zheng, Hong., Zhang, Xi., Li, Chen., Wang, Die., Shen, Yuying., ... & Gao, Hongchang. (2024). BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21. Microbiome, 12(1).
MLA	Zheng, Hong,et al."BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21".Microbiome 12.1(2024).