title: 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.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA.
authors.forename: Liping
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA.
authors.forename: Zhuyu
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA.
authors.forename: Chris
authors.initials: C
authors.lastname: Bosco
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Guidotti
authors.affiliation: Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Xinxiang Medical University, Xinxiang, China.
authors.forename: Mingyong
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of California San Diego, La Jolla, CA.
authors.forename: Mana
authors.initials: M
authors.lastname: Parast
authors.affiliation: Department of Microbiology, University of Colorado School of Medicine, Aurora, CO.
authors.forename: Jerome
authors.initials: J
authors.lastname: Schaack
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO.
authors.forename: William W
authors.initials: WW
authors.lastname: Hay
authors.affiliation: Department of Reproductive Medicine, University of California San Diego, La Jolla, CA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Moore
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, CA jishao@ucsd.edu.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Shao
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics; D002460:Cell Line; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D044343:Overnutrition / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D014327:Trophoblasts
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D018955:CD36 Antigens; C000602680:FABPpm protein, mouse; C493409:Fabp3 protein, mouse; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D005230:Fatty Acids, Nonesterified; D047495:PPAR gamma; D012333:RNA, Messenger; D011973:Receptors, LDL; D014280:Triglycerides; C036053:VLDL receptor; D005992:Glycerol-3-Phosphate O-Acyltransferase; C571223:glycerol-3-phosphate acyltransferase 2, mouse; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C000602679:GPAT3 protein, mouse; D008071:Lipoprotein Lipase; C447939:SIRT1 protein, human; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1