Lipid Metabolism Is Dysregulated before, during and after Pregnancy in a Mouse Model of Gestational Diabetes.
Lipid Metabolism Is Dysregulated before, during and after Pregnancy in a Mouse Model of Gestational Diabetes.
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DOI：
10.3390/ijms22147452
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发表时间：
2021-07-12
影响因子：
5.6
通讯作者：
Ozanne SE
中科院分区：
文献类型：
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作者：
Furse S;Fernandez-Twinn DS;Chiarugi D;Koulman A;Ozanne SE
本研究的目的是检验这一假设，即母体脂质代谢在正常妊娠期间受到调节，而这些调节在妊娠期糖尿病（GDM）中发生改变。我们测试了这一假设，使用一个既定的小鼠模型的饮食诱导的肥胖与妊娠相关的糖耐量丧失和一种新的脂质分析工具，脂质交通分析，使用脂质的时间分布，以确定通过时间过程中的脂质代谢控制的差异。我们的研究结果表明，怀孕的开始与脂质代谢的几个变化有关，包括与新生脂肪生成相关的变量较少，循环中含PUFA的脂质较少。健康妊娠中的一些脂质代谢变化不太明显，或者在发生GDM的母鼠中发生得更晚。肥胖GDM组母体脂质代谢的一些变化是如此之晚，以至于只发生在对照组母鼠的系统开始向非妊娠状态切换时。这些结果表明，脂质代谢的调制在健康的妊娠和这些变化的时间是改变GDM妊娠。这些发现提出了关于脂质代谢如何影响健康妊娠期间代谢变化的重要问题。此外，由于脂质体的改变在葡萄糖耐量丧失之前就存在，它们可能在机制上有助于GDM的发展。
The aim of the current study was to test the hypothesis that maternal lipid metabolism was modulated during normal pregnancy and that these modulations are altered in gestational diabetes mellitus (GDM). We tested this hypothesis using an established mouse model of diet-induced obesity with pregnancy-associated loss of glucose tolerance and a novel lipid analysis tool, Lipid Traffic Analysis, that uses the temporal distribution of lipids to identify differences in the control of lipid metabolism through a time course. Our results suggest that the start of pregnancy is associated with several changes in lipid metabolism, including fewer variables associated with de novo lipogenesis and fewer PUFA-containing lipids in the circulation. Several of the changes in lipid metabolism in healthy pregnancies were less apparent or occurred later in dams who developed GDM. Some changes in maternal lipid metabolism in the obese-GDM group were so late as to only occur as the control dams’ systems began to switch back towards the non-pregnant state. These results demonstrate that lipid metabolism is modulated in healthy pregnancy and the timing of these changes is altered in GDM pregnancies. These findings raise important questions about how lipid metabolism contributes to changes in metabolism during healthy pregnancies. Furthermore, as alterations in the lipidome are present before the loss of glucose tolerance, they could contribute to the development of GDM mechanistically.