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A gut microbial metabolite of dietary polyphenols reverses obesity-driven hepatic steatosis.

Authors :
Osborn LJ
Schultz K
Massey W
DeLucia B
Choucair I
Varadharajan V
Banerjee R
Fung K
Horak AJ 3rd
Orabi D
Nemet I
Nagy LE
Wang Z
Allende DS
Willard BB
Sangwan N
Hajjar AM
McDonald C
Ahern PP
Hazen SL
Brown JM
Claesen J
Source :
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Nov 29; Vol. 119 (48), pp. e2202934119. Date of Electronic Publication: 2022 Nov 23.
Publication Year :
2022

Abstract

The molecular mechanisms by which dietary fruits and vegetables confer cardiometabolic benefits remain poorly understood. Historically, these beneficial properties have been attributed to the antioxidant activity of flavonoids. Here, we reveal that the host metabolic benefits associated with flavonoid consumption hinge, in part, on gut microbial metabolism. Specifically, we show that a single gut microbial flavonoid catabolite, 4-hydroxyphenylacetic acid (4-HPAA), is sufficient to reduce diet-induced cardiometabolic disease (CMD) burden in mice. The addition of flavonoids to a high fat diet heightened the levels of 4-HPAA within the portal plasma and attenuated obesity, and continuous delivery of 4-HPAA was sufficient to reverse hepatic steatosis. The antisteatotic effect was shown to be associated with the activation of AMP-activated protein kinase α (AMPKα). In a large survey of healthy human gut metagenomes, just over one percent contained homologs of all four characterized bacterial genes required to catabolize flavonols into 4-HPAA. Our results demonstrate the gut microbial contribution to the metabolic benefits associated with flavonoid consumption and underscore the rarity of this process in human gut microbial communities.

Details

Language :
English
ISSN :
1091-6490
Volume :
119
Issue :
48
Database :
MEDLINE
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
36417437
Full Text :
https://doi.org/10.1073/pnas.2202934119