Hepatocyte growth factor is elevated in amniotic fluid from obese women and regulates placental glucose and fatty acid metabolism.

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.

Decreased mitochondrial fatty acid oxidation in placentas from women with preeclampsia.

Preeclampsia is a leading cause of maternal and fetal morbidity and mortality in high and low-income countries. The aetiology of preeclampsia is multifactorial and remains obscure. Some evidences suggest that altered placental fatty acid oxidation might play a role in the pathogenesis of preeclampsia. To reveal if placental fatty acid oxidation is reduced in preeclampsia, we evaluate the expression levels of enzymes of mitochondrial fatty acid oxidation using quantitative Real-time PCR and the fatty acid oxidation rate in placental explants. We found that long-chain 3-hydroxyacyl-CoA dehydrogenase levels and fatty acid oxidation capacity were significantly reduced in placentas from women with preeclampsia.