The Choline Metabolite TMAO Inhibits NETosis and Promotes Placental Development in GDM of Humans and Mice
The Choline Metabolite TMAO Inhibits NETosis and Promotes Placental Development in GDM of Humans and Mice
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胆碱代谢物 TMAO 抑制人类和小鼠 GDM 中的 NETosis 并促进胎盘发育
DOI：
10.2337/db21-0188
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发表时间：
2021-07
期刊：
影响因子：
7.7
通讯作者：
Xiao Xiaoqiu
中科院分区：
文献类型：
--
作者：
Lin Xiaojing;Zhang Yunqi;He Xiaoling;Chen Yan;Chen Nan;Liu Juncheng;Wang Miaoran;Li Yue;Yang Hong;Fan Lei;Hou Yi;Li Jibin;Wu Chaodong;Qi Hongbo;Zhang Hua;Xiao Xiaoqiu
胆碱代谢物三甲胺n -氧化物（TMAO）已被认为是妊娠期糖尿病（GDM）的危险因素，但其在GDM中的确切作用尚未报道。在这项研究中，我们将重点放在胎盘发育上，以揭示TMAO在GDM中的作用。我们发现GDM女性外周血浆和脐带血浆TMAO水平升高，TMAO水平与新生儿体重和胎盘厚度呈正相关。外周和脐带血浆中的中性粒细胞胞外陷阱（NETs）以及GDM女性胎盘中的髓过氧化物酶表达也增加。net可以抑制HTR-8/Svneo细胞的增殖、迁移、侵袭和血管生成。然而，TMAO不仅可以抑制NETs的形成，还可以增强HTR-8/Svneo细胞的生物学功能。在nets缺失的PAD4−/−和野生型小鼠中诱导GDM， PAD4−/−小鼠的胎盘重量显著增加。TMAO喂养也抑制了NETs的形成，进一步增加了胎盘和胎儿的重量，但这种增加并不影响胎盘的结构。我们的数据表明，较高的TMAO水平和异常NETs的形成与GDM有关。TMAO不仅能促进胎盘和胎儿的发育，还能抑制NETs的形成。
Choline metabolite trimethylamine N-oxide (TMAO) has been recognized as a risk factor of gestational diabetes mellitus (GDM), but its exact role in GDM has not been reported. In this study, we focused on the placenta development to reveal the role of TMAO in GDM. We found that the TMAO levels in peripheral and cord plasma were increased in women with GDM and that TMAO levels were positively correlated with newborn weight and placental thickness. Neutrophil extracellular traps (NETs) in the peripheral and cord plasma and the myeloperoxidase expression in the placenta of women with GDM also increased. NETs could inhibit the proliferation, migration, invasion, and angiogenesis of HTR-8/Svneo cells. However, TMAO not only could inhibit the formation of NETs but also could enhance the biological function of HTR-8/Svneo cells. With induction of GDM in NETs-deficient PAD4−/− and wild-type mice, the placental weight of PAD4−/− mice increased significantly. TMAO feeding also inhibited the formation of NETs and further increased the weight of the placenta and fetuses, and this increase did not affect the placental structure. Our data indicate that higher TMAO levels and the formation of abnormal NETs were associated with GDM. TMAO not only could promote the development of the placenta and fetuses but also could inhibit the formation of NETs.
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影响因子：
5.8
作者：
Palmai-Pallag, Timea;Bachrati, Csanad Z.
通讯作者：
Bachrati, Csanad Z.
妊娠早期三甲胺 N-氧化物代谢物与妊娠糖尿病风险：巢式病例对照研究
影响因子：
5.8
作者：
Huo, Xiaoxu;Li, Jing;Yang, Xilin
通讯作者：
Yang, Xilin
DOI：
10.3945/jn.115.211136
发表时间：
2015-05
期刊：
The Journal of nutrition
影响因子：
--
作者：
Carly E Visentin;S. Masih;L. Plumptre;O. Malysheva;Daiva E. Nielsen;K. Sohn;A. Ly;A. Lausman;H. Berger;R. Croxford;A. El-Sohemy;M. Caudill;D. O’Connor;Young-In Kim
通讯作者：
Carly E Visentin;S. Masih;L. Plumptre;O. Malysheva;Daiva E. Nielsen;K. Sohn;A. Ly;A. Lausman;H. Berger;R. Croxford;A. El-Sohemy;M. Caudill;D. O’Connor;Young-In Kim
影响因子：
4.5
作者：
Barzilay, Eran;Moon, Ashley;Berger, Howard
通讯作者：
Berger, Howard
影响因子：
44.1
作者：
Remijsen, Quinten;Vanden Berghe, Tom;Vandenabeele, Peter
通讯作者：
Vandenabeele, Peter