Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function.
Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function.
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DOI：
10.3390/ijms19103228
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发表时间：
2018-10-19
影响因子：
5.6
通讯作者：
Blanco-Vaca F
中科院分区：
文献类型：
--
作者：
Canyelles M;Tondo M;Cedó L;Farràs M;Escolà-Gil JC;Blanco-Vaca F
最近的证据，包括大量的基因表达分析和各种各样的其他多组学方法，证明了肠道微生物区系和血脂调节之间的相互作用。胆碱和L肉碱的肠道微生物代谢导致三甲胺的形成，并伴随肝脏黄素单加氧酶3(FMO3)转化为三甲胺-N-氧化物(TMAO)。血浆TMAO水平是由肠道微生物区系的遗传变异、饮食和组成决定的。多项研究表明，TMAO血浆水平与动脉粥样硬化性血栓性心血管疾病(CVD)的风险之间存在关联。我们的目标是综述TMAO产生和FMO3发挥其致动脉粥样硬化作用的分子途径。TMAO可能通过上调巨噬细胞清道夫受体，解除对肝胆固醇和胆汁酸代谢的调节，损害巨噬细胞的反向胆固醇转运(RCT)，促进泡沫细胞的形成。此外，FMO3可能通过调节参与肝脏脂肪生成和糖异生的多个基因而促进血脂异常。FMO3还损害胆固醇动态平衡的多个方面，包括跨肠道胆固醇输出和巨噬细胞特异性RCT。至少部分FMO3对脂质代谢和动脉粥样硬化的影响似乎不依赖于TMA/TMAO的形成。总体而言，这些发现有可能为肠道微生物区系的治疗操作开辟一个新时代，以提高心血管疾病的风险。
Recent evidence, including massive gene-expression analysis and a wide-variety of other multi-omics approaches, demonstrates an interplay between gut microbiota and the regulation of plasma lipids. Gut microbial metabolism of choline and l-carnitine results in the formation of trimethylamine (TMA) and concomitant conversion into trimethylamine-N-oxide (TMAO) by liver flavin monooxygenase 3 (FMO3). The plasma level of TMAO is determined by the genetic variation, diet and composition of gut microbiota. Multiple studies have demonstrated an association between TMAO plasma levels and the risk of atherothrombotic cardiovascular disease (CVD). We aimed to review the molecular pathways by which TMAO production and FMO3 exert their proatherogenic effects. TMAO may promote foam cell formation by upregulating macrophage scavenger receptors, deregulating enterohepatic cholesterol and bile acid metabolism and impairing macrophage reverse cholesterol transport (RCT). Furthermore, FMO3 may promote dyslipidemia by regulating multiple genes involved in hepatic lipogenesis and gluconeogenesis. FMO3 also impairs multiple aspects of cholesterol homeostasis, including transintestinal cholesterol export and macrophage-specific RCT. At least part of these FMO3-mediated effects on lipid metabolism and atherogenesis seem to be independent of the TMA/TMAO formation. Overall, these findings have the potential to open a new era for the therapeutic manipulation of the gut microbiota to improve CVD risk.
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影响因子：
1.9
作者：
Bushueva O;Solodilova M;Churnosov M;Ivanov V;Polonikov A
通讯作者：
Polonikov A
影响因子：
158.5
作者：
通讯作者：
--
影响因子：
5.2
作者：
Cho, Clara E.;Taesuwan, Siraphat;Caudill, Marie A.
通讯作者：
Caudill, Marie A.
影响因子：
158.5
作者：
Barter, Philip;Gotto, Antonio M.;Fruchart, Jean-Charles
通讯作者：
Fruchart, Jean-Charles
DOI：
10.1073/pnas.1215689109
发表时间：
2012-12-26
影响因子：
11.1
作者：
Craciun, Smaranda;Balskus, Emily P.
通讯作者：
Balskus, Emily P.