Leptin induces mitogenic effect on human choriocarcinoma cell line (JAr) via MAP kinase activation in a glucose-dependent fashion

Leptin and glucose effect on cell growth has been investigated in the JAr human choriocarcinoma cells. When JAr cells were cultured in the presence of 6 mm glucose (LG), proliferation and thymidine incorporation were induced by serum but not by leptin. At variance, at 25 mm glucose (HG), proliferation and thymidine incorporation were stimulated by leptin and serum to a comparable extent. HG culturing also enhanced leptin-stimulated insulin receptor substrate 1 (IRS1) and MAPK phosphorylation. Blockage of MAPK activity with PD98059 caused an inhibition of glucose- and leptin-dependent thymidine incorporation. At variance with HG conditions no effects were observed in cells cultured in 6 mm glucose upon treatment with PD98059. Neither glucose nor leptin determined a modification in leptin receptors total content. In this study, we provide evidence that in placental cells, leptin, similarly to that observed with insulin, stimulates cell proliferation by inducing the IRS1/MAPK pathway in a glucose-dependent fashion. (C) 2003 Elsevier Science Ltd. All rights reserved.