PXD028230-1

PXD028230 is an original dataset announced via ProteomeXchange.

Title	Gut microbiota production of N,N,N-trimethyl-5-aminovaleric acid reduces fatty acid oxidation and accelerates cardiac hypertrophy in diet-induced obesity
Description	Numerous studies found intestinal microbiota alterations which are thought to affect the development of various diseases through the production of gut-derived metabolites. However, the specific metabolites and their pathophysiological contribution to cardiac hypertrophy or heart failure progression still remain unclear. N,N,N-trimethyl-5-aminovaleric acid (TMAVA), derived from trimethyllysine through the gut microbiota, was elevated with gradually increased risk of cardiac mortality and transplantation in a prospective heart failure cohort (n=1647). TMAVA treatment aggravated cardiac hypertrophy and dysfunction in high-fat diet-fed mice. Decreased fatty acid oxidation (FAO) is a hallmark of metabolic reprogramming in the diseased heart and contributes to impaired myocardial energetics and contractile dysfunction. Proteomics uncovered that TMAVA disturbed cardiac energy metabolism, leading to inhibition of FAO and myocardial lipid accumulation. TMAVA treatment altered mitochondrial ultrastructure, respiration and FAO and inhibited carnitine metabolism. Mice with γ-butyrobetaine hydroxylase (BBOX) deficiency displayed a similar cardiac hypertrophy phenotype, indicating that TMAVA functions through BBOX. Finally, exogenous carnitine supplementation reversed TMAVA induced cardiac hypertrophy. These data suggest that the gut microbiota-derived TMAVA is a key determinant for the development of cardiac hypertrophy through inhibition of carnitine synthesis and subsequent FAO.
HostingRepository	iProX
AnnounceDate	2021-09-08
AnnouncementXML	Submission_2021-09-08_20:35:08.382.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mingming Zhao
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-08 20:33:30	ID requested
⏵ 1	2021-09-08 20:35:08	announced
2	2022-10-25 00:20:10	announced	2022-10-25: Update publication information.

Dataset with its publication pending

submitter keyword: TMAVA, cardiac hypertrophy

Lemin Zheng
contact affiliation	Peking University
contact email	zhengl@bjmu.edu.cn
lab head
Mingming Zhao
contact affiliation	Peking University
contact email	zhaomingming@pku.edu.cn
dataset submitter

iProX dataset URI