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

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.

• Authors: Liping Qiao, Zhuyu Guo, Chris Bosco, Stefano Guidotti, Yunfeng Wang, Mingyong Wang, Mana Parast, Jerome Schaack, William W Hay Jr, Thomas R Moore, Jianhua Shao
• Journal: Diabetes (Diabetes) Vol. 64 Issue 9 Pg. 3111-20 (Sep 2015) ISSN: 1939-327X [Electronic] United States
• PMID: 25948680 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• CCAAT-Enhancer-Binding Protein-alpha
• CD36 Antigens
• FABPpm protein, mouse
• Fabp3 protein, mouse
• Fatty Acid Binding Protein 3
• Fatty Acid-Binding Proteins
• Fatty Acids, Nonesterified
• PPAR gamma
• RNA, Messenger
• Receptors, LDL
• Triglycerides
• VLDL receptor
• Glycerol-3-Phosphate O-Acyltransferase
• glycerol-3-phosphate acyltransferase 2, mouse
• 1-Acylglycerol-3-Phosphate O-Acyltransferase
• GPAT3 protein, mouse
• Lipoprotein Lipase
• SIRT1 protein, human
• Sirt1 protein, mouse
• Sirtuin 1

Topics

• 1-Acylglycerol-3-Phosphate O-Acyltransferase (genetics, metabolism)
• Animals
• CCAAT-Enhancer-Binding Protein-alpha (metabolism)
• CD36 Antigens (genetics)
• Cell Line
• Diet, High-Fat
• Disease Models, Animal
• Fatty Acid Binding Protein 3
• Fatty Acid-Binding Proteins (genetics, metabolism)
• Fatty Acids, Nonesterified (blood)
• Female
• Glycerol-3-Phosphate O-Acyltransferase (genetics, metabolism)
• Humans
• Lipoprotein Lipase (metabolism)
• Maternal Exposure
• Mice
• Mice, Inbred C57BL
• Obesity (metabolism)
• Overnutrition (metabolism)
• PPAR gamma (metabolism)
• Placenta (metabolism)
• Pregnancy
• Pregnancy Complications (metabolism)
• RNA, Messenger (metabolism)
• Receptors, LDL (genetics, metabolism)
• Sirtuin 1 (metabolism)
• Triglycerides (blood)
• Trophoblasts