Maternal High-Fat Feeding Increases Placental Lipoprotein Lipase Activity by Reducing SIRT1 Expression in Mice.
Maternal High-Fat Feeding Increases Placental Lipoprotein Lipase Activity by Reducing SIRT1 Expression in Mice.
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作者：
Qiao L;Guo Z;Bosco C;Guidotti S;Wang Y;Wang M;Parast M;Schaack J;Hay WW Jr;Moore TR;Shao J
本研究探讨了母体营养过剩和肥胖如何调节胎盘中促进脂质运输的蛋白质的表达和激活。为了建立母体营养过剩和肥胖模型，在整个妊娠期给C57BL/6小鼠喂食高脂肪（HF）饲料。hf喂养的母鼠的胎儿血清游离脂肪酸和体脂水平显著升高。尽管胎盘重量无显著差异，但高脂饲料喂养的母猪胎盘中脂蛋白脂肪酶（LPL）蛋白水平和活性显著升高。在高频喂养的母鼠胎盘中，甘油三酯含量和CD36、VLDLr、FABP3、FABPpm、GPAT2和-3的mRNA水平也有所增加。虽然HF组胎盘中过氧化物酶体增殖物活化受体-γ (PPARγ)和CCAAT/增强子结合蛋白-α蛋白水平均显著升高，但只有PPARγ对培养的JEG-3人滋养细胞中LPL表达有促进作用。母体喂养HF显著降低胎盘中SIRT1的表达。通过使用SIRT1激活剂和抑制剂以及培养的滋养细胞，证明了SIRT1对LPL表达的抑制作用。我们还发现SIRT1抑制滋养细胞中PPARγ的表达。最重要的是，抑制PPARγ消除了sirt1介导的对LPL表达的调节作用。总之，这些结果表明，母体营养过剩通过降低SIRT1对PPARγ的抑制作用诱导滋养细胞中LPL的表达。
This study investigated how maternal overnutrition and obesity regulate expression and activation of proteins that facilitate lipid transport in the placenta. To create a maternal overnutrition and obesity model, primiparous C57BL/6 mice were fed a high-fat (HF) diet throughout gestation. Fetuses from HF-fed dams had significantly increased serum levels of free fatty acid and body fat. Despite no significant difference in placental weight, lipoprotein lipase (LPL) protein levels and activity were remarkably elevated in placentas from HF-fed dams. Increased triglyceride content and mRNA levels of CD36, VLDLr, FABP3, FABPpm, and GPAT2 and -3 were also found in placentas from HF-fed dams. Although both peroxisome proliferator–activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α protein levels were significantly increased in placentas of the HF group, only PPARγ exhibited a stimulative effect on LPL expression in cultured JEG-3 human trophoblasts. Maternal HF feeding remarkably decreased SIRT1 expression in placentas. Through use of an SIRT1 activator and inhibitor and cultured trophoblasts, an inhibitory effect of SIRT1 on LPL expression was demonstrated. We also found that SIRT1 suppresses PPARγ expression in trophoblasts. Most importantly, inhibition of PPARγ abolished the SIRT1-mediated regulatory effect on LPL expression. Together, these results indicate that maternal overnutrition induces LPL expression in trophoblasts by reducing the inhibitory effect of SIRT1 on PPARγ.