| Literature DB >> 28636934 |
Rebecca C Schugar1, Diana M Shih2, Manya Warrier1, Robert N Helsley1, Amy Burrows1, Daniel Ferguson1, Amanda L Brown1, Anthony D Gromovsky1, Markus Heine3, Arunachal Chatterjee4, Lin Li1, Xinmin S Li1, Zeneng Wang1, Belinda Willard1, YongHong Meng2, Hanjun Kim2, Nam Che2, Calvin Pan2, Richard G Lee5, Rosanne M Crooke5, Mark J Graham5, Richard E Morton6, Carl D Langefeld7, Swapan K Das8, Lawrence L Rudel9, Nizar Zein10, Arthur J McCullough10, Srinivasan Dasarathy11, W H Wilson Tang12, Bernadette O Erokwu13, Chris A Flask13, Markku Laakso14, Mete Civelek15, Sathyamangla V Naga Prasad4, Joerg Heeren3, Aldons J Lusis2, Stanley L Hazen12, J Mark Brown16.
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.Entities:
Keywords: FMO3; adipose; diabetes; flavin-containing monooxygenase 3; microbiota; nutrition; obesity
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Year: 2017 PMID： 28636934 PMCID： PMC5672822 DOI： 10.1016/j.celrep.2017.05.077
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423