title: Hepatocyte growth factor is elevated in amniotic fluid from obese women and regulates placental glucose and fatty acid metabolism.
abstract: BACKGROUND
  To evaluate the impact of the pro-inflammatory cytokine hepatocyte growth factor (HGF) on the regulation of glucose and lipid placental metabolism.
  
  
  METHODS
  HGF levels were quantified in amniotic fluid and placenta from control and obese women. 2-deoxy-glucose (2-DOG) uptake, glycolysis, fatty acid oxidation (FAO), fatty acid esterification, de novo fatty acid synthesis, triglyceride levels and carnitine palmitoyltransferase activities (CPT) were measured in placental explants upon addition of pathophysiological HGF levels.
  
  
  RESULTS
  In obese women, total- and -activated-HGF levels in amniotic fluid were elevated ∼24%, and placental HGF levels were ∼3-fold higher than in control women. At a similar dose to that present in amniotic fluid of obese women, HGF (30 ng/mL) increased Glut-1 levels and 2-DOG uptake by ∼25-30% in placental explants. HGF-mediated effect on 2-DOG uptake was dependent on the activation of phosphatidylinositol 3-kinase signaling pathway. In addition, HGF decreased ∼20% FAO, whereas esterification and de novo fatty acid synthesis increased ∼15% and ∼25% respectively, leading to 2-fold triglyceride accumulation in placental explants. In parallel, HGF reduced CPT-I activity ∼70%.
  
  
  CONCLUSIONS
  HGF is a cytokine elevated in amniotic fluid and placental tissue of obese women, which through its ability to stimulate 2-DOG uptake and metabolism impairs FAO and enhances esterification and de novo fatty acid synthesis, leading to accumulation of placental triglycerides.
authors.affiliation: Research Unit, Puerta del Mar University Hospital, Cádiz, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Visiedo
authors.affiliation: Department of Obstetrics and Gynecology, Puerta del Mar University Hospital, Cádiz, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Bugatto
authors.affiliation: Clinical Analysis Department, Puerta del Mar University Hospital, Cádiz, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Carrasco-Fernández
authors.affiliation: Clinical Analysis Department, Puerta del Mar University Hospital, Cádiz, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Sáez-Benito
authors.affiliation: Research Unit, Puerta del Mar University Hospital, Cádiz, Spain.
authors.forename: R M
authors.initials: RM
authors.lastname: Mateos
authors.affiliation: Research Unit, Puerta del Mar University Hospital, Cádiz, Spain; Instituto de Genética y Biología Molecular (Universidad de Valladolid-CSIC), Valladolid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Cózar-Castellano
authors.affiliation: Department of Obstetrics and Gynecology, Puerta del Mar University Hospital, Cádiz, Spain; Department of Obstetrics and Gynecology, La Paz University Hospital, Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Bartha
authors.affiliation: Research Unit, Puerta del Mar University Hospital, Cádiz, Spain; University of Castilla-La Mancha, School of Environmental Sciences and Biochemistry, Toledo, Spain. Electronic address: perdomogm@yahoo.com.
authors.forename: G
authors.initials: G
authors.lastname: Perdomo
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism*; D001692:Biological Transport; D015992:Body Mass Index; D002585:Cesarean Section; D003430:Cross-Sectional Studies; D004734:Energy Metabolism; D004951:Esterification; D005227:Fatty Acids / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D009765:Obesity / Q000378:metabolism*; D009924:Organ Culture Techniques; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D005227:Fatty Acids; C066855:HGF protein, human; D014280:Triglycerides; D017228:Hepatocyte Growth Factor; D005947:Glucose
keywords: Fatty acid metabolism; Glucose metabolism; Hepatocyte growth factor; Placental inflammation