A Makkar1, T Mishima2, G Chang3, C Scifres2, Y Sadovsky4. 1. Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Department of Pediatrics, University of Pittsburgh, USA. 2. Magee-Womens Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA. 3. 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. 4. 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.
Abstract
INTRODUCTION: 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.
INTRODUCTION: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: Alfonso Gil-Sánchez; Elvira Larqué; Hans Demmelmair; María I Acien; Fabienne L Faber; Juan J Parrilla; Berthold Koletzko Journal: Am J Clin Nutr Date: 2010-05-05 Impact factor: 7.045