Maternal High-Fat Feeding Increases Placental Lipoprotein Lipase Activity by Reducing SIRT1 Expression in Mice

  • Liping Qiao
    Department of Pediatrics, University of California San Diego, La Jolla, CA
  • Zhuyu Guo
    Department of Pediatrics, University of California San Diego, La Jolla, CA
  • Chris Bosco
    Department of Pediatrics, University of California San Diego, La Jolla, CA
  • Stefano Guidotti
    Department of Pediatrics, University of California San Diego, La Jolla, CA
  • Yunfeng Wang
    Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China
  • Mingyong Wang
    Xinxiang Medical University, Xinxiang, China
  • Mana Parast
    Department of Pathology, University of California San Diego, La Jolla, CA
  • Jerome Schaack
    Department of Microbiology, University of Colorado School of Medicine, Aurora, CO
  • William W. Hay
    Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
  • Thomas R. Moore
    Department of Reproductive Medicine, University of California San Diego, La Jolla, CA
  • Jianhua Shao
    Department of Pediatrics, University of California San Diego, La Jolla, CA

抄録

<jats:p>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.</jats:p>

収録刊行物

  • Diabetes

    Diabetes 64 (9), 3111-3120, 2015-05-06

    American Diabetes Association

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