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. 2015 Dec 15;309(12):R1569-77.
doi: 10.1152/ajpregu.00385.2015. Epub 2015 Oct 21.

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

Affiliations

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

Paula Díaz et al. Am J Physiol Regul Integr Comp Physiol. .

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.

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Figures

Fig. 1.
Fig. 1.
Expression of fatty acid translocase (FAT)/CD36 and fatty acid transport protein (FATP) 2, FATP 4, and FATP 6 in trophoblast plasma membrane (TPM) from control (C) and obese (OB) dams. Representative immunoblots with corresponding histograms illustrating relative protein expression of FAT/CD36 (A), FATP 2 (B), FATP 4 (C), and FATP 6 (D). E: placental mRNA expression of Fat/Cd36, Fatp 2, 4, and 6 normalized to the geometric mean of Gadph and Tfrc mRNA. Data are expressed as means + SE; n = 10/group. Statistical significance was determined using Student's unpaired t-test, *P < 0.05.
Fig. 2.
Fig. 2.
Activity and expression of regulators of placental fatty acid uptake. A: lipase activity in TPM from C and OB dams. B: representative immunoblots with corresponding histogram illustrating relative placental protein expression of PPARγ in homogenate from C and OB dams. C: placental mRNA expression of Pparγ and Lpl normalized to the geometric mean of Gadph and Tfrc mRNA. D: representative immunoblots with corresponding histogram illustrating relative placental protein expression of (S112) pPPARγ in homogenate from C and OB dams. Values are expressed as means + SE; n = 10/group. Statistical significance was determined using Student's unpaired t-test.
Fig. 3.
Fig. 3.
Placental mRNA expression of PPARγ-regulated genes and other transcription factors involved in lipid metabolism. mRNA expression of Ldhb, Pcx, Dgat1, Dcakd, Srebp1c, and C/Ebpα in C and OB dams normalized to the geometric mean of Gadph and Tfrc mRNA. Values are expressed as means + SE; n = 10/group. Statistical significance was determined using Student's unpaired t-test.
Fig. 4.
Fig. 4.
Placental expression of FABPs 1, 3–5 in homogenate from C and OB dams. Representative immunoblots with corresponding histograms illustrating relative protein expression of FABP 1 (A), FABP 3 (B), FABP 4 (C) and FABP 5 (D). E: placental mRNA expression of Fabps 1, 3–5 normalized to the geometric mean of Gadph and Tfrc mRNA. Data are expressed as means + SE; n = 10/group. Statistical significance was determined using Student's unpaired t-test, *P < 0.01.
Fig. 5.
Fig. 5.
Lipid accumulation in fetal livers. Representative sections from fetal liver from C (A) and OB (B) dams stained for Oil Red O. C: corresponding histogram illustrating fetal liver lipid droplet number. Values are expressed as means + SE; n = 14/group. Statistical significance was determined using Student's unpaired t-test, *P < 0.05.

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