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

2017; Cell Press; Volume: 19; Issue: 12 Linguagem: Inglês

10.1016/j.celrep.2017.05.077

2639-1856

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, Yonghong Meng, Han‐Jun Kim, Nam Che, Calvin Pan, Richard Lee, Rosanne M. Crooke, Mark J. Graham, Richard E. Morton, Carl D. Langefeld, Swapan K. Das, Lawrence L. Rudel, Nizar N. Zein, Arthur J. McCullough, Srinivasan Dasarathy, W.H. Wilson Tang, Bernadette O. Erokwu, Chris A. Flask, Markku Laakso, Mete Civelek, Sathyamangla V. Naga Prasad, Jöerg Heeren, Aldons J. Lusis, Stanley L. Hazen, J. Mark Brown,

Tryptophan and brain disorders

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.