Pregnancy, a state of insulin resistance (IR), is associated with elevated levels of cytokines and profound alterations in metabolism, directed towards supplying adequate nutrition for the fetus. Adiponectin, an adipokine with anti-inflammatory and insulin sensitising properties, plays an important role in energy homeostasis. Interestingly, in gestational diabetes mellitus (GDM), a state of greater insulin resistance, serum adiponectin levels are lower than normal subjects. We hypothesised that the human placenta is a source of adiponectin, and we investigated its expression, secretion, and regulation. The study was approved by the Local Research Ethics Committee and all patients involved gave their informed consent.
Adiponectin gene is present in the human term placenta, with expression primarily in the syncytiotrophoblast. Radioimmuno-analysis of conditioned media from explant experiments revealed that the placenta can secrete adiponectin in vitro. Addition of conditioned media to HEK-293 cells transfected with adiponectin receptor-1 altered the phosphorylation status of ERK1/2 and p38 MAPK, an effect abolished after preabsorption with adiponectin antibody.
Cytokines including TNF-α, IFN-γ, IL-6 and leptin, differentially modulated placental adiponectin receptors as well as adiponectin gene expression and secretion. Interestingly, in GDM placentae, there was a significant downregulation of adiponectin and adipoR2, but not adipoR1 mRNA.
Our results indicate the novel production and secretion of adiponectin from the human placenta, differential regulation by cytokines and altered expression in GDM. Collectively, our data suggest that adiponectin may play a role in adapting energy metabolism at the materno-fetal interface.
01 - 05 Apr 2006
European Society of Endocrinology