Modulation of Cholesterol Transport by Insulin-Treated Gestational Diabetes Mellitus in Human Full-Term Placenta
Modulation of Cholesterol Transport by Insulin-Treated Gestational Diabetes Mellitus in Human Full-Term Placenta
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DOI：
10.1095/biolreprod.112.105619
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发表时间：
2013-01-01
影响因子：
3.6
通讯作者：
Lafond, Julie
中科院分区：
文献类型：
--
作者：
Dube, Evemie;Ethier-Chiasson, Maude;Lafond, Julie
妊娠期糖尿病（GDM）是一种常见的妊娠并发症，其特征是葡萄糖耐受不良，导致血脂异常，并因肥胖而加重。胆固醇作为脂蛋白的一部分通过清道夫受体B类I型受体（SRBI）、低密度脂蛋白受体（LDLR）和极低密度脂蛋白受体（VLDLR）被胎盘摄取，然后由ABCA 1和ABCG 1介导其流出。PCSK 9参与LDLR和VLDLR的降解。本研究的目的是评估GDM和孕前体重指数（BMI）对胆固醇转运的影响，通过调节几个关键因素的表达。在分娩时从正常体重的无GDM女性（n = 10）、正常体重的GDM女性（n = 6）和超重/肥胖的GDM女性（n = 6）获得人足月胎盘、母体和静脉脐带血样品。评价血液样本中的脂质（总胆固醇、高密度脂蛋白、低密度脂蛋白、甘油三酯、游离脂肪酸、载脂蛋白A1、载脂蛋白B100）水平。信使RNA和蛋白质表达水平（LDLR，VLDLR，SRBI，ABCA 1，ABCG 1，前蛋白转化酶枯草杆菌蛋白酶/kexin 9型，肝脏x受体，过氧化物酶体增殖物激活受体）分别在人类足月胎盘中进行评估，通过实时RT-PCR和Western印迹。使用商业试剂盒对组织匀浆评价脂蛋白脂肪酶活性。总的来说，我们的研究表明，GDM影响母体和新生儿的脂质谱，以及胎盘胆固醇从母体转移到胎儿循环的不同关键参与者，这取决于母体BMI。这些变化可能会影响胎儿的代谢，并使胎儿未来易患代谢性疾病。
Gestational diabetes mellitus (GDM) is a common complication of pregnancy that is characterized by glucose intolerance, leads to dyslipidemia, and is aggravated by obesity. Cholesterol is taken up by the placenta as part of lipoproteins through the scavenger receptor class B type I receptor (SRBI), low-density lipoprotein receptor (LDLR), and very low density lipoprotein receptor (VLDLR), and its efflux is then mediated by ABCA1 and ABCG1. PCSK9 is involved in the degradation of LDLR and VLDLR. The goal of this study was to evaluate the impact of GDM and prepregnancy body mass index (BMI) on cholesterol transport through the modulation of the expression of several key players. Human full-term placenta, maternal, and venous cord blood samples were obtained at delivery from normal-weight women without GDM (n = 10), normal-weight women with GDM (n = 6), and overweight/obese women with GDM (n = 6). Lipids (total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, free fatty acids, apolipoprotein A1, apolipoprotein B100) levels were evaluated in blood samples. Messenger RNA and protein expression levels (LDLR, VLDLR, SRBI, ABCA1, ABCG1, proprotein convertase subtilisin/kexin type 9, liver x receptors, peroxisome proliferator-activated receptors) were assessed in human full-term placenta, respectively, by real-time RT-PCR and Western blots. Lipoprotein lipase activity was evaluated using a commercial kit on tissue homogenates. Overall, our study demonstrates that GDM affects the maternal and neonatal lipid profiles as well as different key players of placental cholesterol transfer from the maternal to the fetal circulation, depending on the maternal BMI. These changes could affect the fetal metabolism and predispose the fetus to future metabolic diseases.