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

Authors: Liu, Ken H; Owens, Joshua A; Saeedi, Bejan; Cohen, Catherine E; Bellissimo, Moriah P; Naudin, Crystal; Darby, Trevor; Druzak, Samuel; Maner-Smith, Kristal; Orr, Michael; Hu, Xin; Fernandes, Jolyn; Camacho, Mary Catherine; Hunter-Chang, Sarah; VanInsberghe, David; Ma, Chunyu; Ganesh, Thota; Yeligar, Samantha M; Uppal, Karan; Go, Young-Mi; Alvarez, Jessica A; Vos, Miriam B; Ziegler, Thomas R; Woodworth, Michael H; Kraft, Colleen S; Jones, Rheinallt M; Ortlund, Eric; Neish, Andrew S; Jones, Dean P

Published In Nat Metab, (2021 Dec)

Abstract: 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.

PubMed ID: 34931082 Exiting the NIEHS site

MeSH Terms: Adiposity; Animals; Diet, Western; Energy Metabolism*; Fatty Acids/metabolism; Gastrointestinal Microbiome; Host Microbial Interactions*; Humans; Lipid Metabolism; Liver/metabolism; Mice; Microbiota*; Mitochondria/metabolism; Obesity/etiology; Obesity/metabolism*; Oxidation-Reduction

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