The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue.
The TMAO-Producing Enzyme Flavin-Containing Monooxygenase 3 Regulates Obesity and the Beiging of White Adipose Tissue.
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DOI：
10.1016/j.celrep.2017.05.077
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发表时间：
2017-06-20
期刊：
影响因子：
8.8
通讯作者：
Brown JM
中科院分区：
文献类型：
--
作者：
Schugar RC;Shih DM;Warrier M;Helsley RN;Burrows A;Ferguson D;Brown AL;Gromovsky AD;Heine M;Chatterjee A;Li L;Li XS;Wang Z;Willard B;Meng Y;Kim H;Che N;Pan C;Lee RG;Crooke RM;Graham MJ;Morton RE;Langefeld CD;Das SK;Rudel LL;Zein N;McCullough AJ;Dasarathy S;Tang WHW;Erokwu BO;Flask CA;Laakso M;Civelek M;Naga Prasad SV;Heeren J;Lusis AJ;Hazen SL;Brown JM
新的证据表明，人类肠道中的微生物是导致肥胖相关疾病的关键环境因素。在这里，我们证明肠道微生物启动的三甲胺-N-氧化物（TMAO）生成途径与肥胖和能量代谢有关。在多个临床队列中，观察到 TMAO 的全身水平与 2 型糖尿病密切相关。此外，循环TMAO水平与杂交小鼠多样性小组中不同近交系的肥胖特征相关。此外，反义寡核苷酸介导的 TMAO 产生酶、含黄素单加氧酶 3 (FMO3) 的敲低或基因删除，可赋予小鼠预防肥胖的保护作用。小鼠和人体研究表明 FMO3 对白色脂肪组织的米色化具有负调节作用。总的来说，我们的研究揭示了 TMAO 产生酶 FMO3 与肥胖和白色脂肪组织的米色之间的联系。
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.
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影响因子：
10.5
作者：
Brown JM;Hazen SL
通讯作者：
Hazen SL
影响因子：
64.5
作者：
Muoio DM
通讯作者：
Muoio DM
影响因子：
3.7
作者：
Lever M;George PM;Slow S;Bellamy D;Young JM;Ho M;McEntyre CJ;Elmslie JL;Atkinson W;Molyneux SL;Troughton RW;Frampton CM;Richards AM;Chambers ST
通讯作者：
Chambers ST
影响因子：
64.5
作者：
Puigserver, P;Wu, ZD;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
6.5
作者：
Brown, J. Mark;Betters, Jenna L.;Yu, Liqing
通讯作者：
Yu, Liqing