title: Fatty acid binding protein-4 is expressed in the mouse placental labyrinth, yet is dispensable for placental triglyceride accumulation and fetal growth.
abstract: BACKGROUND
  Fatty Acid Binding Protein-4 (FABP4) is a member of a family of FABP proteins that regulate intracellular lipid trafficking in diverse tissues. We recently showed that FABP4 regulates triglyceride accumulation in primary human trophoblasts. To assess the function of placental FABP4 in vivo, we tested the hypothesis that FABP4 is expressed in the murine placenta, and regulates placenta triglyceride accumulation.
  
  
  METHODS
  C57Bl/6 wild type or Fabp4-null mice were time-bred, and fetuses and placentas harvested at different time points during pregnancy. Placental FABP4 expression was assessed at different gestational ages, using quantitative PCR, immunohistochemistry, immunofluorescence and western immunoblotting. FABPs expression was examined by RT-qPCR. Placental lipids were extracted using the Folch method and triglyceride levels determined using a colorimetric quantification kit.
  
  
  RESULTS
  Using immunohistochemistry, we found that FABP4 was expressed in the placental labyrinthine layer, predominantly in endothelial cells in association with CD31 positive fetal capillaries. The level of placental FABP4 mRNA and protein increased from E12.5 to E16.5 and slightly decreased at E18.5. Breeding of Fabp4 heterozygous mice resulted in embryonic genotypes that followed a Mendelian distribution and exhibited normal weight and morphology, triglyceride content, and expression of other FABP family members. Exposure to hypoxia (O2 = 12%) between E12.5-E18.5 did not uncover a difference between wild type and Fabp4-null mice.
  
  
  CONCLUSIONS
  FABP4 is expressed in the mouse placental labyrinth, with highest expression at E16.5. FABP4 is dispensable for feto-placental growth and placental lipid accumulation.
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, University of Pittsburgh, USA.
authors.forename: A
authors.initials: A
authors.lastname: Makkar
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Mishima
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Tsinghua University School of Medicine Education Program, Beijing, China.
authors.forename: G
authors.initials: G
authors.lastname: Chang
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Scifres
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: rideoutl@mwri.magee.edu.
authors.forename: Y
authors.initials: Y
authors.lastname: Sadovsky
mesh_terms: D000818:Animals; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D014280:Triglycerides / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism
chemical_list: C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D014280:Triglycerides
keywords: FABP4; Fatty acids; Fetus; Triglycerides; Trophoblast
references.citation: Fertil Steril. 2011 Jun 30;95(8):2749-52.e1-5
references.pmid: 21704217
references.citation: Proc Natl Acad Sci U S A. 1986 Jun;83(11):4021-5
references.pmid: 3459166
references.citation: Am J Clin Nutr. 2000 Jan;71(1 Suppl):285S-91S
references.pmid: 10617984
references.citation: Diabetologia. 2013 Jan;56(1):10-21
references.pmid: 23052058
references.citation: Am J Clin Nutr. 2010 Jul;92(1):115-22
references.pmid: 20444955
references.citation: Curr Opin Clin Nutr Metab Care. 2014 Mar;17(2):151-5
references.pmid: 24468708
references.citation: Semin Perinatol. 1989 Apr;13(2):118-30
references.pmid: 2662412
references.citation: J Lipid Res. 1999 May;40(5):967-72
references.pmid: 10224167
references.citation: Eur J Obstet Gynecol Reprod Biol. 1995 Jul;61(1):57-62
references.pmid: 8549848
references.citation: J Nutr. 2004 Sep;134(9):2464S-2468S
references.pmid: 15333743
references.citation: Science. 1996 Nov 22;274(5291):1377-9
references.pmid: 8910278
references.citation: Prog Lipid Res. 2009 Jan;48(1):52-61
references.pmid: 19041341
references.citation: Am J Clin Nutr. 2000 Jan;71(1 Suppl):315S-22S
references.pmid: 10617989
references.citation: Int J Obes (Lond). 2011 Feb;35(2):217-25
references.pmid: 20603627
references.citation: Am J Clin Nutr. 2011 Dec;94(6 Suppl):1908S-1913S
references.pmid: 21562082
references.citation: Endocrine. 2002 Oct;19(1):43-55
references.pmid: 12583601
references.citation: J Biol Chem. 1985 May 10;260(9):5563-7
references.pmid: 3988766
references.citation: Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R312-9
references.pmid: 19923363
references.citation: Endocrinology. 2014 Mar;155(3):1099-106
references.pmid: 24424031
references.citation: J Biol Chem. 1957 May;226(1):497-509
references.pmid: 13428781
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2012 Jan-Feb;86(1-2):13-20
references.pmid: 22115845
references.citation: Diabetes. 2000 Jun;49(6):904-11
references.pmid: 10866041
references.citation: Diabetes Metab Res Rev. 2000 May-Jun;16(3):202-10
references.pmid: 10867720
references.citation: Prog Lipid Res. 2001 Jan-Mar;40(1-2):1-94
references.pmid: 11137568
references.citation: J Clin Endocrinol Metab. 2011 Jul;96(7):E1083-91
references.pmid: 21525163
references.citation: J Clin Endocrinol Metab. 2004 Sep;89(9):4607-14
references.pmid: 15356070
references.citation: Placenta. 2012 Nov;33 Suppl 2:e30-4
references.pmid: 22809673
references.citation: Ann N Y Acad Sci. 2002 Jun;967:299-310
references.pmid: 12079857
references.citation: PLoS One. 2011;6(10):e25865
references.pmid: 22028793
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2012 Jan-Feb;86(1-2):39-49
references.pmid: 22093549
references.citation: Am J Obstet Gynecol. 2007 Nov;197(5):516.e1-6
references.pmid: 17826730
references.citation: Annu Rev Nutr. 2010 Aug 21;30:237-55
references.pmid: 20438366
references.citation: Front Genet. 2011 Sep 06;2:57
references.pmid: 22303352