Microbial metabolite delta-valerobetaine is a diet-dependent obesogen.

Autor: Liu KH; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Owens JA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA., Saeedi B; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Cohen CE; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA., Bellissimo MP; Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Naudin C; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA., Darby T; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA., Druzak S; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA., Maner-Smith K; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA., Orr M; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Hu X; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Fernandes J; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Camacho MC; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Hunter-Chang S; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., VanInsberghe D; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Ma C; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Ganesh T; Department of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA, USA., Yeligar SM; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Atlanta Veterans Affairs Health Care System, Decatur, GA, USA., Uppal K; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Go YM; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Alvarez JA; Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Vos MB; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA., Ziegler TR; Division of Endocrinology, Metabolism, and Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Woodworth MH; Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Kraft CS; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.; Division of Infectious Disease, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Jones RM; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA., Ortlund E; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA., Neish AS; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA. aneish@emory.edu., Jones DP; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA. dpjones@emory.edu.
Jazyk: angličtina
Zdroj: Nature metabolism [Nat Metab] 2021 Dec; Vol. 3 (12), pp. 1694-1705. Date of Electronic Publication: 2021 Dec 20.
DOI: 10.1038/s42255-021-00502-8
Abstrakt: Obesity and obesity-related metabolic disorders are linked to the intestinal microbiome. However, the causality of changes in the microbiome-host interaction affecting energy metabolism remains controversial. Here, we show the microbiome-derived metabolite δ-valerobetaine (VB) is a diet-dependent obesogen that is increased with phenotypic obesity and is correlated with visceral adipose tissue mass in humans. VB is absent in germ-free mice and their mitochondria but present in ex-germ-free conventionalized mice and their mitochondria. Mechanistic studies in vivo and in vitro show VB is produced by diverse bacterial species and inhibits mitochondrial fatty acid oxidation through decreasing cellular carnitine and mitochondrial long-chain acyl-coenzyme As. VB administration to germ-free and conventional mice increases visceral fat mass and exacerbates hepatic steatosis with a western diet but not control diet. Thus, VB provides a molecular target to understand and potentially manage microbiome-host symbiosis or dysbiosis in diet-dependent obesity.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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