@article{d009a6663dcb4f54b62a75da97a0ca55,
title = "The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue",
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.",
keywords = "adipose, diabetes, flavin-containing monooxygenase 3, FMO3, microbiota, nutrition, obesity",
author = "Schugar, {Rebecca C.} and Shih, {Diana M.} and Manya Warrier and Helsley, {Robert N.} and Amy Burrows and Daniel Ferguson and Brown, {Amanda L.} and Gromovsky, {Anthony D.} and Markus Heine and Arunachal Chatterjee and Lin Li and Li, {Xinmin S.} and Zeneng Wang and Belinda Willard and Meng, {Yong Hong} and Hanjun Kim and Nam Che and Calvin Pan and Lee, {Richard G.} and Crooke, {Rosanne M.} and Graham, {Mark J.} and Morton, {Richard E.} and Langefeld, {Carl D.} and Das, {Swapan K.} and Rudel, {Lawrence L.} and Nizar Zein and McCullough, {Arthur J.} and Srinivasan Dasarathy and Tang, {W. H.Wilson} and Erokwu, {Bernadette O.} and Flask, {Chris A.} and Markku Laakso and Mete Civelek and {Naga Prasad}, {Sathyamangla V.} and Joerg Heeren and Lusis, {Aldons J.} and Hazen, {Stanley L.} and Brown, {J. Mark}",
note = "Funding Information: This work was supported by NIH and Office of Dietary Supplements grants R00 HL096166 (J.M.B.), R01 HL122283 (J.M.B.), P50 AA024333 (J.M.B.), R01 HL103866 (S.L.H.), R01 HL126827 (S.L.H. and W.H.W.T), R01 DK106000 (S.L.H. and W.H.W.T), R01 HL130819 (Z.W.), R01 DK090111 (S.K.D.), R00 HL12172 (M.C.), P01 HL028481 (A.J.L.), P01 HL030568-31A1 (A.J.L. and D.M.S.), and P01 HL49373 (L.L.R.), as well as by the Deutsche Forschungsgemeinschaft in the framework of SFB841 (J.H.), the Academy of Finland and the Finnish Cardiovascular Research Foundation (M.L.), and the American Heart Association (postdoctoral fellowship 15POST2535000 to R.C.S., postdoctoral fellowship 14POST18700001 to M.W., and postdoctoral fellowship 17POST3285000 to R.N.H.). Publisher Copyright: {\textcopyright} 2017 The Authors",
year = "2017",
month = jun,
day = "20",
doi = "10.1016/j.celrep.2017.05.077",
language = "English",
volume = "19",
pages = "2451--2461",
journal = "Cell Reports",
issn = "2211-1247",
number = "12",
}