Increased placental fatty acid transporter 6 and binding protein 3 expression and fetal liver lipid accumulation in a mouse model of obesity in pregnancy.
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.
Department of Pediatrics, Section of Neonatology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado; Department of Obstetrics and Gynecology, University of Texas Health Science Center San Antonio, San Antonio, Texas paula.diaz-rodriguez@ucdenver.edu.
Paula
P
Díaz
Department of Obstetrics and Gynecology, University of Texas Health Science Center San Antonio, San Antonio, Texas.
Jessica
J
Harris
Department of Obstetrics and Gynecology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado; and.
Fredrick J
FJ
Rosario
Department of Pediatrics, Section of Neonatology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado; Department of Obstetrics and Gynecology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado; and.
Theresa L
TL
Powell
Department of Obstetrics and Gynecology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado; and.
Thomas
T
Jansson
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D059305:Diet, High-Fat; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D000074026:Fatty Acid Binding Protein 3; D050612:Fatty Acid Transport Proteins / Q000235:genetics / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005865:Gestational Age; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D018955:CD36 Antigens; D019422:Dietary Sucrose; C543322:FATP6 protein, mouse; C493409:Fabp3 protein, mouse; D000074026:Fatty Acid Binding Protein 3; D050612:Fatty Acid Transport Proteins; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D008049:Lipase
fatty acid; fatty acid transport protein; maternal-fetal exchange; trophoblast