Laboratory of Reproduction and Metabolism, CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th floor, 1121ABG Buenos Aires, Argentina.
J Mol Endocrinol. 2011 Jun 17;47(1):1-12. doi: 10.1530/JME-10-0173. Print 2011 Aug.
Maternal diabetes impairs fetoplacental metabolism and growth. Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor capable of regulating lipid metabolism and inflammatory pathways. In this study, we analyzed whether placental and fetal PPARα activation regulates lipid metabolism and nitric oxide (NO) production in term placentas from diabetic rats. Diabetes was induced by neonatal streptozotocin administration. On day 21 of pregnancy, placentas from control and diabetic rats were cultured in the presence of PPARα agonists (clofibrate and leukotriene B(4) (LTB(4))) for further evaluation of levels, synthesis, and peroxidation of lipids as well as NO production. Besides, on days 19, 20, and 21 of gestation, fetuses were injected with LTB(4), and the placentas were explanted on day 21 of gestation for evaluation of placental weight and concentrations of placental lipids, lipoperoxides, and NO metabolites. We found that placentas from diabetic rats showed reduced PPARα concentrations. They presented no lipid overaccumulation but reduced lipid synthesis, parameters negatively regulated by PPARα activators. Lipid peroxidation and NO production, increased in placentas from diabetic rats, were negatively regulated by PPARα activators. Fetal PPARα activation in diabetic rats does not change placental lipid concentrations but reduced placental weight and NO production. In conclusion, PPARα activators regulate lipid metabolism and NO production in term placentas from diabetic rats, an activation that regulates placental growth and can partly be exerted by the developing fetus.
母体糖尿病会损害胎儿胎盘的代谢和生长。过氧化物酶体增殖物激活受体 α（PPARα）是一种核受体，能够调节脂质代谢和炎症途径。在这项研究中，我们分析了胎盘和胎儿 PPARα 的激活是否调节了来自糖尿病大鼠的足月胎盘中的脂质代谢和一氧化氮（NO）的产生。糖尿病是通过新生大鼠链脲佐菌素给药诱导的。在妊娠第 21 天，对照组和糖尿病组大鼠的胎盘在 PPARα 激动剂（氯贝特和白三烯 B4（LTB4））的存在下进行培养，以进一步评估脂质的水平、合成和过氧化以及 NO 的产生。此外，在妊娠第 19、20 和 21 天，胎儿被注射 LTB4，胎盘在妊娠第 21 天被取出用于评估胎盘重量以及胎盘脂质、脂过氧化物和 NO 代谢物的浓度。我们发现，糖尿病大鼠的胎盘 PPARα 浓度降低。它们没有出现脂质过度积累，但脂质合成减少，这是 PPARα 激活剂负调控的参数。糖尿病大鼠胎盘的脂质过氧化和 NO 产生增加，这被 PPARα 激活剂负调控。在糖尿病大鼠中，胎儿 PPARα 的激活并没有改变胎盘脂质的浓度，但减少了胎盘重量和 NO 的产生。总之，PPARα 激活剂调节了来自糖尿病大鼠的足月胎盘中的脂质代谢和 NO 产生，这种激活调节了胎盘的生长，并且可以部分由发育中的胎儿来发挥作用。
