Fecal microbiome transplantation and tributyrin improves early cardiac dysfunction and modifies the BCAA metabolic pathway in a diet induced pre-HFpEF mouse model.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_6A9DC5CC0889
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fecal microbiome transplantation and tributyrin improves early cardiac dysfunction and modifies the BCAA metabolic pathway in a diet induced pre-HFpEF mouse model.
Journal
Frontiers in cardiovascular medicine
Author(s)
Hatahet J., Cook T.M., Bonomo R.R., Elshareif N., Gavini C.K., White C.R., Jesse J., Mansuy-Aubert V., Aubert G.
ISSN
2297-055X (Print)
ISSN-L
2297-055X
Publication state
Published
Issued date
02/2023
Peer-reviewed
Oui
Volume
10
Pages
1105581
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
More than 50% of patients with heart failure present with heart failure with preserved ejection fraction (HFpEF), and 80% of them are overweight or obese. In this study we developed an obesity associated pre-HFpEF mouse model and showed an improvement in both systolic and diastolic early dysfunction following fecal microbiome transplant (FMT). Our study suggests that the gut microbiome-derived short-chain fatty acid butyrate plays a significant role in this improvement. Cardiac RNAseq analysis showed butyrate to significantly upregulate ppm1k gene that encodes protein phosphatase 2Cm (PP2Cm) which dephosphorylates and activates branched-chain α-keto acid dehydrogenase (BCKDH) enzyme, and in turn increases the catabolism of branched chain amino acids (BCAAs). Following both FMT and butyrate treatment, the level of inactive p-BCKDH in the heart was reduced. These findings show that gut microbiome modulation can alleviate early cardiac mechanics dysfunction seen in the development of obesity associated HFpEF.
Keywords
branched chain amino acids (BCAAs), gut microbiome, heart failure with preserved ejection fraction, obesity, short chain fatty acids
Pubmed
Web of science
Open Access
Yes
Create date
13/03/2023 18:16
Last modification date
23/01/2024 8:27
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