Fatty Acid Binding Protein-4 is expressed in the mouse placental labyrinth, yet is dispensable for placental triglyceride accumulation and fetal growth

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.

Elevated Glucose and Insulin Levels Decrease DHA Transfer across Human Trophoblasts via SIRT1-Dependent Mechanism

“…The expression of FABP3 and FABP4 were increased in trophoblasts from GDM conditions. FABP3 and FABP4 are among the major fatty acid-binding proteins that function as intracellular lipid chaperones to shuttle fatty acids from the maternal side of the plasma membrane to target organelles (i.e., to mitochondria for oxidation and for storage as lipid droplets) or to the basal side of the membrane for delivery to the fetus [52][53][54]. FABP3 and FABP4 have been shown to have a higher binding affinity to DHA and other long-chain polyunsaturated fatty acids [55,56].…”

FABP4 in Gestational Diabetes—Association between Mothers and Offspring

“…Among the nutrients that support intrauterine growth, fatty acids are important, especially during the second half of pregnancy, when fetal growth accelerates and fat accretion increases exponentially [54]. Importantly, Makkar et al found that perinatal hypoxia selectively upregulated the expression of FABP1, FABP3, and FABP4 and that fatty acids enhance the expression of FABP4 [54]. Coupled with the known function of FABP4 as a fatty acid chaperone, Makkar et al hypothesized that FABP4 could be a key regulator of trophoblastic lipid transport and accumulation.…”

Fatty Acid-Binding Protein 4 (FABP4): Pathophysiological Insights and Potent Clinical Biomarker of Metabolic and Cardiovascular Diseases

“…38 It has been reported that FABPs, including FABP4, are expressed in human placental trophoblasts and that FABP4 is a key regulator of trophoblastic lipid transport and accumulation during placental development. [134][135][136] FABP4 was detected in apoptotic granulosa cells in atretic antral follicles of the mouse ovary, 137 suggesting a possible relevance to polycystic ovary syndrome (PCOS), which is known to frequently coexist with insulin resistance. Expression of Fabp4 mRNA in isolated granulosa cells was higher in patients with PCOS than in controls.…”