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A gut microbial metabolite of dietary polyphenols reverses obesity-driven hepatic steatosis.
Osborn, Lucas J; Schultz, Karlee; Massey, William; DeLucia, Beckey; Choucair, Ibrahim; Varadharajan, Venkateshwari; Banerjee, Rakhee; Fung, Kevin; Horak, Anthony J; Orabi, Danny; Nemet, Ina; Nagy, Laura E; Wang, Zeneng; Allende, Daniela S; Willard, Belinda B; Sangwan, Naseer; Hajjar, Adeline M; McDonald, Christine; Ahern, Philip P; Hazen, Stanley L; Brown, J Mark; Claesen, Jan.
Afiliación
  • Osborn LJ; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Schultz K; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Massey W; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195.
  • DeLucia B; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Choucair I; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Varadharajan V; College of Arts and Sciences, John Carroll University, University Heights, OH 44118.
  • Banerjee R; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Fung K; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Horak AJ; Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195.
  • Orabi D; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Nemet I; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Nagy LE; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Wang Z; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Allende DS; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Willard BB; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Sangwan N; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Hajjar AM; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • McDonald C; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Ahern PP; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Hazen SL; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Brown JM; Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
  • Claesen J; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44195.
Proc Natl Acad Sci U S A ; 119(48): e2202934119, 2022 11 29.
Article en En | MEDLINE | ID: mdl-36417437
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.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Hígado Graso / Microbioma Gastrointestinal Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2022 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Hígado Graso / Microbioma Gastrointestinal Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2022 Tipo del documento: Article