The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue

Rebecca C. Schugar, Diana M. Shih, Manya Warrier, Robert N. Helsley, Amy Burrows, Daniel Ferguson, Amanda L. Brown, Anthony D. Gromovsky, Markus Heine, Arunachal Chatterjee, Lin Li, Xinmin S. Li, Zeneng Wang, Belinda Willard, Yong Hong Meng, Hanjun Kim, Nam Che, Calvin Pan, Richard G. Lee, Rosanne M. CrookeMark J. Graham, Richard E. Morton, Carl D. Langefeld, Swapan K. Das, Lawrence L. Rudel, Nizar Zein, Arthur J. McCullough, Srinivasan Dasarathy, W. H.Wilson Tang, Bernadette O. Erokwu, Chris A. Flask, Markku Laakso, Mete Civelek, Sathyamangla V. Naga Prasad, Joerg Heeren, Aldons J. Lusis, Stanley L. Hazen, J. Mark Brown

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Emerging evidence suggests that microbes resident in the human intestine represent a key environmental factor contributing to obesity-associated disorders. Here, we demonstrate that the gut microbiota-initiated trimethylamine N-oxide (TMAO)-generating pathway is linked to obesity and energy metabolism. In multiple clinical cohorts, systemic levels of TMAO were observed to strongly associate with type 2 diabetes. In addition, circulating TMAO levels were associated with obesity traits in the different inbred strains represented in the Hybrid Mouse Diversity Panel. Further, antisense oligonucleotide-mediated knockdown or genetic deletion of the TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) conferred protection against obesity in mice. Complimentary mouse and human studies indicate a negative regulatory role for FMO3 in the beiging of white adipose tissue. Collectively, our studies reveal a link between the TMAO-producing enzyme FMO3 and obesity and the beiging of white adipose tissue.

Original languageEnglish
Pages (from-to)2451-2461
Number of pages11
JournalCell Reports
Volume19
Issue number12
DOIs
StatePublished - Jun 20 2017

Keywords

  • adipose
  • diabetes
  • flavin-containing monooxygenase 3
  • FMO3
  • microbiota
  • nutrition
  • obesity

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