title: Fatty acid binding protein 4 regulates intracellular lipid accumulation in human trophoblasts.
abstract: BACKGROUND
  Maternal obesity, gestational diabetes (GDM), or type 2 diabetes (T2DM) is associated with altered lipid metabolism and fetal overgrowth.
  
  
  OBJECTIVE
  The objective of the study was to test the hypothesis that hyperlipidemia and hyperinsulinemia regulate lipid content and expression of lipid-trafficking proteins in human placental trophoblasts.
  
  
  METHODS
  Pregnant women were prospectively enrolled for clinical specimens collection, and cultured human trophoblasts were used for experiments.
  
  
  METHODS
  This was a translational study conducted at an academic biomedical research center.
  
  
  METHODS
  Normal weight, obese, or obese with gestational diabetes or type 2 diabetes pregnant women (n = 10 in each group) undergoing scheduled cesarean delivery at term were enrolled.
  
  
  METHODS
  Cultured primary human trophoblasts, exposed to insulin (10 nM) and/or fatty acids mix (1200 μM) in the absence or presence of an fatty acid binding protein 4 (FABP4) inhibitor or after small interfering RNA-mediated knockdown of FABP4.
  
  
  METHODS
  Serum lipid levels were analyzed in the maternal venous and fetal cord blood. Placental biopsies and cultured trophoblasts were analyzed for FABP expression and lipid accumulation.
  
  
  RESULTS
  Obese diabetic women and their fetuses had elevated serum triglyceride levels. Nonesterified fatty acids were elevated and triglycerides were reduced in placental villi from obese diabetic women, and this was accompanied by a 2.6-fold increase in FABP4 expression (P < 0.05). In primary human trophoblasts, fatty acids markedly increased the expression of FABP4 (20- to 40-fold, P < 0.05) and cellular triglyceride content (4-fold, P < 0.05), and this effect was attenuated by small interfering RNA-mediated knockdown of FABP4 or the selective FABP4 inhibitor BMS309403.
  
  
  CONCLUSIONS
  Hyperlipidemia alters lipid content and increases the expression of FABP4 in trophoblasts. The reduced triglyceride content after FABP4 inhibition suggests that FABP4 is essential for trophoblast lipid accumulation.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Scifres
authors.forename: Baosheng
authors.initials: B
authors.lastname: Chen
authors.forename: D Michael
authors.initials: DM
authors.lastname: Nelson
authors.forename: Yoel
authors.initials: Y
authors.lastname: Sadovsky
mesh_terms: D000328:Adult; D001713:Biphenyl Compounds / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D016640:Diabetes, Gestational / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism / Q000502:physiology*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D011247:Pregnancy; D011720:Pyrazoles / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: C559288:2-(2'-(5-ethyl-3,4-diphenyl-1H-pyrazol-1-yl)biphenyl-3-yloxy)acetic acid; D001713:Biphenyl Compounds; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D007328:Insulin; D011720:Pyrazoles