Increased placental fatty acid transporter 6 and binding protein 3 expression and fetal liver lipid accumulation in a mouse model of obesity in pregnancy

Am J Physiol Regul Integr Comp Physiol. 2015 Dec 15;309(12):R1569-77. doi: 10.1152/ajpregu.00385.2015. Epub 2015 Oct 21.

Abstract

Obesity in pregnancy is associated with increased fetal growth and adiposity, which, in part, is determined by transplacental nutrient supply. Trophoblast uptake and intracellular trafficking of lipids are dependent on placental fatty acid transport proteins (FATP), translocase (FAT/CD36), and fatty acid binding proteins (FABP). We hypothesized that maternal obesity in mice leads to increased placental expression of FAT/CD36, FATPs, and FABPs, and lipid accumulation in the fetal liver. C57/BL6J female mice were fed either a control (C; n = 10) or an obesogenic (OB; n = 10) high-fat, high-sugar diet before mating and throughout pregnancy. At E18.5, placentas and fetal livers were collected. Trophoblast plasma membranes (TPM) were isolated from placental homogenates. Expression of FAT/CD36 and FATP (TPM) and FABP (homogenates) was determined by immunoblotting. Gene expression was assessed by RT-quantitative PCR. Sections of fetal livers were stained for Oil Red O, and lipid droplets were quantified. TPM protein expression of FAT/CD36, FATP 2, and FATP 4 was comparable between C and OB groups. Conversely, TPM FATP 6 expression was increased by 35% in OB compared with C placentas without changes in mRNA expression. FABPs 1, 3-5 and PPARγ were expressed in homogenates, and FABP 3 expression increased 27% in OB compared with C placentas; however, no changes were observed in mRNA expression. Lipid droplet accumulation was 10-fold higher in the livers of fetuses from OB compared with C group. We propose that increased lipid transport capacity in obese mice promotes transplacental fatty acid transport and contributes to excess lipid accumulation in the fetal liver.

Keywords: fatty acid; fatty acid transport protein; maternal-fetal exchange; trophoblast.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD36 Antigens / metabolism
  • Diet, High-Fat
  • Dietary Sucrose
  • Disease Models, Animal
  • Fatty Acid Binding Protein 3
  • Fatty Acid Transport Proteins / genetics
  • Fatty Acid Transport Proteins / metabolism*
  • Fatty Acid-Binding Proteins / genetics
  • Fatty Acid-Binding Proteins / metabolism*
  • Fatty Liver / etiology
  • Fatty Liver / genetics
  • Fatty Liver / metabolism*
  • Fatty Liver / pathology
  • Female
  • Gestational Age
  • Lipase / metabolism
  • Lipid Metabolism*
  • Liver / metabolism*
  • Liver / pathology
  • Mice, Inbred C57BL
  • Obesity / complications
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / pathology
  • PPAR gamma / metabolism
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy Complications / genetics
  • Pregnancy Complications / metabolism*
  • Pregnancy Complications / pathology
  • RNA, Messenger / metabolism
  • Up-Regulation

Substances

  • CD36 Antigens
  • Dietary Sucrose
  • FATP6 protein, mouse
  • Fabp3 protein, mouse
  • Fatty Acid Binding Protein 3
  • Fatty Acid Transport Proteins
  • Fatty Acid-Binding Proteins
  • PPAR gamma
  • RNA, Messenger
  • Lipase