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Cited by 75Pregnancy and preeclampsia studiesBirth, Development, and HealthLipid metabolism and disorders

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

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Qiao, Liping, Guo, Zhuyu, Bosco, Chris, Guidotti, Stefano, Wang, Yunfeng, Wang, Mingyong, Parast, Mana, Schaack, Jerome +3 more·2015·Diabetes
DOI 10.2337/db14-1627PMC PMC4542442
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Abstract

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.

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  • The effects of high-fat diet on placental lipid handling are associated with increased PPARγ and reduced SIRT1 expression, suggesting transcriptional reprogramming of placental lipid handling in maternal obesity.

    “These effects were associated with increased PPARγ and reduced SIRT1 expression—two reciprocal regulators of lipid metabolism—suggesting transcriptional reprogramming of placental lipid handling in maternal obesity.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [53]

  • A high-fat diet upregulates placental lipoprotein lipase and fatty acid transporters CD36 and VLDLr, elevating triglyceride content and fetal free fatty acids.

    “Complementary findings by Qiao et al. (2015) demonstrated that a high-fat diet upregulates placental lipoprotein lipase (LPL) and fatty acid transporters (CD36, VLDLr), elevating triglyceride content and fetal free fatty acids [53].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [53]

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Cited by

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Authors
Qiao, L., Guo, Z., Bosco, C., Guidotti, S., Wang, Y., Wang, M., Parast, M., Schaack, J., Hay, W. W., Moore, T. R., & Shao, J.
Affiliations
  • University of California San Diego (US)
  • China-Japan Friendship Hospital (CN)
  • Henan Medical University (CN)
  • University of Colorado Anschutz (US)
Corresponding author
Shao, Jianhua
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2015-05-06
Volume
64
Issue
9
Pages
3111-3120
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db14-1627
PMC
PMC4542442
OpenAlex
W2213203628
Cited by
75
References
3
Citations by year
2026: 5 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 2 · 2020: 15 · 2019: 8 · 2018: 12 · 2017: 9 · 2016: 3 · 2015: 2
FWCI
9.86
Type
journal article
Language
en
Open access
Licence
www.diabetesjournals.org/site/license (vor, 300 d)
Locations
  • Diabetes (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
National Institutes of Health (DK095132, HD069634)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
maternal high-fat diet, SIRT1, PPARγ, maternal overnutrition, maternal obesity, trophoblast, CD36, FABP3, FABPpm, GPAT3, VLDL receptor, free fatty acids, gestational nutrition
MeSH terms
Fatty Acid Binding Protein 3, Animals, Cell Line, Disease Models, Animal, Fatty Acids, Nonesterified, Female, Glycerol-3-Phosphate O-Acyltransferase, Humans, Lipoprotein Lipase, Mice, Inbred C57BL, Obesity, Placenta, Pregnancy, Pregnancy Complications, Receptors, LDL, RNA, Messenger, Triglycerides, Trophoblasts, Maternal Exposure, CD36 Antigens, CCAAT-Enhancer-Binding Protein-alpha, Overnutrition, PPAR gamma, Fatty Acid-Binding Proteins, 1-Acylglycerol-3-Phosphate O-Acyltransferase, Mice, Sirtuin 1, Diet, High-Fat

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