4.8 Article

Microbial metabolite delta-valerobetaine is a diet-dependent obesogen

Journal

NATURE METABOLISM
Volume 3, Issue 12, Pages 1694-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s42255-021-00502-8

Keywords

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Funding

  1. Georgia Clinical and Translational Science Alliance [UL1 TR002378]
  2. Emory-Georgia Tech Predictive Health Institute
  3. Center for Health Discovery and Well-Being
  4. [T32 GM008602]
  5. [P30 ES019776]
  6. [R01 ES023485]
  7. [U2C ES030163]
  8. [R2C DK118619]
  9. [S10 OD018006]
  10. [K01 DK102851]
  11. [R03 DK117246]
  12. [K24 DK096574]
  13. [R21HD089056]
  14. [R00AA021803]
  15. [R01AA026086]
  16. [R01AI064462]

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Delta-valerobetaine, a microbiome-derived metabolite, correlates with obesity-related phenotypes in humans and exacerbates diet-induced obesity in mice.
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 delta-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. Delta-valerobetaine is a microbiome-derived metabolite that correlates with obesity-related phenotypes in humans, and exacerbates diet-induced obesity in mice.

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