Effect of Flavin-Containing Monooxygenase Genotype, Mouse Strain, and Gender on Trimethylamine N-oxide Production, Plasma Cholesterol Concentration, and an Index of Atherosclerosis.
Effect of Flavin-Containing Monooxygenase Genotype, Mouse Strain, and Gender on Trimethylamine N-oxide Production, Plasma Cholesterol Concentration, and an Index of Atherosclerosis.
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DOI：
10.1124/dmd.117.077636
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Shephard EA
中科院分区：
文献类型：
--
作者：
Veeravalli S;Karu K;Scott F;Fennema D;Phillips IR;Shephard EA
该研究的目的是确定小鼠中含黄素单加氧酶（FMO）家族成员对三甲胺（TMA） n-氧化物（TMAO）产生的贡献，TMAO是一种潜在的致动脉粥样硬化分子，以及在正常饮食条件下，TMAO产生的差异是否与血浆胆固醇浓度的变化或动脉粥样硬化指数（Als）有关。在10周龄的雄性和雌性C57BL/6J和CD-1小鼠以及缺乏各种Fmo基因（Fmo1−/−、2−/−、4−/−和Fmo5−/−）的小鼠系中测量尿TMA、TMAO和血浆胆固醇浓度。在雌性小鼠中，大多数TMA n -氧合由FMO3催化，但在两性中，11%-12%的TMA由FMO1转化为TMAO。性别、Fmo基因型和菌株相关的TMAO产生差异对血浆胆固醇浓度有相反的影响。血浆胆固醇与TMAO生成和尿TMAO浓度呈弱负相关。Fmo基因型对Als无影响。Als与TMAO生成或尿TMAO浓度之间没有相关性。我们的研究结果表明，在正常饮食条件下，氧化三甲胺不会增加血浆胆固醇或作为一种促动脉粥样硬化分子。
The objectives of the study were to determine the contribution, in mice, of members of the flavin-containing monooxygenase (FMO) family to the production of trimethylamine (TMA) N-oxide (TMAO), a potential proatherogenic molecule, and whether under normal dietary conditions differences in TMAO production were associated with changes in plasma cholesterol concentration or with an index of atherosclerosis (Als). Concentrations of urinary TMA and TMAO and plasma cholesterol were measured in 10-week-old male and female C57BL/6J and CD-1 mice and in mouse lines deficient in various Fmo genes (Fmo1−/−, 2−/−, 4−/−, and Fmo5−/−). In female mice most TMA N-oxygenation was catalyzed by FMO3, but in both genders 11%–12% of TMA was converted to TMAO by FMO1. Gender-, Fmo genotype-, and strain-related differences in TMAO production were accompanied by opposite effects on plasma cholesterol concentration. Plasma cholesterol was negatively, but weakly, correlated with TMAO production and urinary TMAO concentration. Fmo genotype had no effect on Als. There was no correlation between Als and either TMAO production or urinary TMAO concentration. Our results indicate that under normal dietary conditions TMAO does not increase plasma cholesterol or act as a proatherogenic molecule.
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DOI：
10.1124/dmd.116.070615
发表时间：
2016-11
期刊：
Drug metabolism and disposition: the biological fate of chemicals
影响因子：
--
作者：
Fennema D;Phillips IR;Shephard EA
通讯作者：
Shephard EA
DOI：
10.1111/j.1432-1033.1996.00683.x
发表时间：
1996-02-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
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