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

被引：220

作者：

Schugar, Rebecca C. ^{[1
,19
]}

Shih, Diana M. ^{[16
,17
,18
]}

Warrier, Manya ^{[1
,19
]}

Helsley, Robert N. ^{[1
,19
]}

Burrows, Amy ^{[1
,19
]}

Ferguson, Daniel ^{[1
,19
]}

Brown, Amanda L. ^{[1
,19
]}

Gromovsky, Anthony D. ^{[1
,19
]}

Heine, Markus ^{[15
]}

Chatterjee, Arunachal

Li, Lin ^{[1
]}

Li, Xinmin S. ^{[1
,19
]}

Wang, Zeneng ^{[1
,19
]}

Willard, Belinda ^{[1
,19
]}

Meng, YongHong ^{[16
,17
,18
]}

Kim, Hanjun ^{[16
,17
,18
]}

Che, Nam ^{[16
,17
,18
]}

Pan, Calvin ^{[16
,17
,18
]}

Lee, Richard G. ^{[8
]}

Crooke, Rosanne M. ^{[8
]}

Graham, Mark J. ^{[8
]}

Morton, Richard E. ^{[1
]}

Langefeld, Carl D. ^{[5
]}

Das, Swapan K. ^{[6
]}

Rudel, Lawrence L. ^{[7
]}

Zein, Nizar ^{[2
]}

McCullough, Arthur J. ^{[2
]}

Dasarathy, Srinivasan ^{[3
]}

Tang, W. H. Wilson ^{[1
,19
,20
]}

Erokwu, Bernadette O. ^{[12
,13
,14
]}

Flask, Chris A. ^{[12
,13
,14
]}

Laakso, Markku ^{[9
,10
]}

Civelek, Mete ^{[11
]}

Prasad, Sathyamangla V. Naga ^{[4
]}

Heeren, Joerg ^{[15
]}

Lusis, Aldons J. ^{[16
,17
,18
]}

Hazen, Stanley L. ^{[1
,19
,20
]}

Brown, J. Mark ^{[1
,19
]}

机构：

[1] Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44195 USA

[2] Cleveland Clin, Dept Gastroenterol & Hepatol, Cleveland, OH 44195 USA

[3] Cleveland Clin, Dept Pathobiol, Cleveland, OH 44195 USA

[4] Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44195 USA

[5] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA

[6] Wake Forest Univ, Sch Med, Dept Endocrinol & Metab, Winston Salem, NC 27157 USA

[7] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA

[8] Ionis Pharmaceut Inc, Cardiovasc Grp, Antisense Drug Discovery, Carlsbad, CA 92010 USA

[9] Univ Eastern Finland, Internal Med, Inst Clin Med, FI-92010 Kuopio, Finland

[10] Kuopio Univ Hosp, F-92010 Kuopio, Finland

[11] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22904 USA

[12] Case Western Reserve Univ, Dept Radiol, Cleveland, OH 44195 USA

[13] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44195 USA

[14] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44195 USA

[15] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, Martinistr 52, D-20246 Hamburg, Germany

[16] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA

[17] Univ Calif Los Angeles, Dept Microbiol, Los Angeles, CA 90095 USA

[18] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA

[19] Cleveland Clin, Ctr Microbiome & Human Hlth, Cleveland, OH 44195 USA

[20] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44195 USA

来源：

CELL REPORTS | 2017年 / 19卷 / 12期

基金：

芬兰科学院;

关键词：

TRIMETHYLAMINE-N-OXIDE; INSULIN SENSITIVITY; HEART-FAILURE; MICROBIAL-METABOLISM; GENETIC-REGULATION; AFRICAN-AMERICANS; GLUCOSE-TOLERANCE; PROGNOSTIC VALUE; GUT MICROBIOTA; L-CARNITINE;

D O I：

10.1016/j.celrep.2017.05.077

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：2451 / 2461

页数：11

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