F Visiedo1, F Bugatto2, C Carrasco-Fernández3, A Sáez-Benito3, R M Mateos1, I Cózar-Castellano4, J L Bartha5, G Perdomo6. 1. Research Unit, Puerta del Mar University Hospital, Cádiz, Spain. 2. Department of Obstetrics and Gynecology, Puerta del Mar University Hospital, Cádiz, Spain. 3. Clinical Analysis Department, Puerta del Mar University Hospital, Cádiz, Spain. 4. Research Unit, Puerta del Mar University Hospital, Cádiz, Spain; Instituto de Genética y Biología Molecular (Universidad de Valladolid-CSIC), Valladolid, Spain. 5. Department of Obstetrics and Gynecology, Puerta del Mar University Hospital, Cádiz, Spain; Department of Obstetrics and Gynecology, La Paz University Hospital, Madrid, Spain. 6. 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.
Abstract
INTRODUCTION: 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%. DISCUSSION: 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.
INTRODUCTION: 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 obesewomen. 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 obesewomen, 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 obesewomen, 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%. DISCUSSION: HGF is a cytokine elevated in amniotic fluid and placental tissue of obesewomen, 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.