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母体肥胖、妊娠糖尿病和脂肪因子对脂肪组织中脂质代谢相关基因表达的影响。

Effect of pre-existing maternal obesity, gestational diabetes and adipokines on the expression of genes involved in lipid metabolism in adipose tissue.

机构信息

Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.

出版信息

Metabolism. 2014 Feb;63(2):250-62. doi: 10.1016/j.metabol.2013.10.001. Epub 2013 Oct 24.

DOI:10.1016/j.metabol.2013.10.001
PMID:24262292
Abstract

OBJECTIVE

To determine the effect of maternal obesity, gestational diabetes mellitus (GDM) and adipokines on the expression of genes involved in fatty acid uptake, transport, synthesis and metabolism.

MATERIALS/METHODS: Human subcutaneous and omental adipose tissues were obtained from lean, overweight and obese normal glucose tolerant (NGT) women and women with GDM. Quantitative RT-PCR (qRT-PCR) was performed to determine the level of expression. Adipose tissue explants were performed to determine the effect of the adipokines TNFα, IL-1β and leptin on adipose tissue gene expression.

RESULTS

Pre-existing maternal obesity and GDM are associated with decreased expression in genes involved in fatty acid uptake and intracellular transport (LPL, FATP2, FATP6, FABPpm and ASCL1), triacylglyceride (TAG) biosynthesis (MGAT1,7 MGAT2 and DGAT1), lipogenesis (FASN) and lipolysis (PNPLA2, HSL and MGLL). Decreased gene expression was also observed for the transcription factors involved in lipid metabolism (LXRα, PPARα, PPARδ, PPARγ, RXRα and SREBP1c). On the other hand, the gene expression of the adipokines TNFα, IL-1β and or leptin was increased in adipose tissue from obese and GDM women. Functional in vitro studies revealed that these adipokines decreased the gene expression of LPL, FATP2, FATP6, ASCL1, PNPLA2, PPARδ, PPARγ and RXRα.

CONCLUSIONS

Pregnancies complicated by pre-existing maternal obesity and GDM are associated with abnormal adipose tissue lipid metabolism, which may play a role in the pathogenesis of these diseases.

摘要

目的

确定母体肥胖、妊娠糖尿病(GDM)和脂肪因子对脂肪酸摄取、转运、合成和代谢相关基因表达的影响。

材料/方法:从瘦、超重和肥胖糖耐量正常(NGT)的女性以及患有 GDM 的女性中获得人体皮下和网膜脂肪组织。采用实时定量 RT-PCR(qRT-PCR)检测表达水平。进行脂肪组织外植体实验以确定脂肪因子 TNFα、IL-1β 和瘦素对脂肪组织基因表达的影响。

结果

先前存在的母体肥胖和 GDM 与脂肪酸摄取和细胞内转运(LPL、FATP2、FATP6、FABPpm 和 ASCL1)、三酰基甘油(TAG)生物合成(MGAT1、7MGAT2 和 DGAT1)、脂肪生成(FASN)和脂肪分解(PNPLA2、HSL 和 MGLL)相关基因的表达减少有关。参与脂质代谢的转录因子(LXRα、PPARα、PPARδ、PPARγ、RXRα 和 SREBP1c)的基因表达也减少了。另一方面,肥胖和 GDM 女性的脂肪组织中脂肪因子 TNFα、IL-1β 和瘦素的基因表达增加。功能体外研究表明,这些脂肪因子降低了 LPL、FATP2、FATP6、ASCL1、PNPLA2、PPARδ、PPARγ 和 RXRα 的基因表达。

结论

伴有先前存在的母体肥胖和 GDM 的妊娠与异常的脂肪组织脂质代谢有关,这可能在这些疾病的发病机制中起作用。

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