Leptin in embryos from control and diabetic rats during organogenesis: a modulator of nitric oxide production and lipid homeostasis

Abstract

Leptin is involved in many metabolic and reproductive events and its levels are altered by the diabetic pathology. In this study, leptin concentrations and leptin effects on both nitric oxide (NO) and lipid concentrations were investigated in embryos from control and diabetic rats. Diabetes was induced by neonatal streptozotocin administration (90 mg/kg). Embryos from control and diabetic rats were obtained on days 10.5 and 13.5 of gestation, corresponding to early organogenesis and post-placentation periods respectively. Leptin was analysed by enzyme immunoanalysis and immunohistochemistry. Nitrates and nitrites were assessed as an index of NO production. Lipid concentrations were analysed by thin layer chromatography. Leptin concentrations were decreased in embryos obtained from diabetic rats on days 10.5 and 13.5 of gestation when compared to controls. NO concentrations, elevated in diabetic embryopathy, were diminished in the presence of leptin in the embryos obtained from control and diabetic animals both during early organogenesis and after placentation. Leptin additions reduced phospholipid, cholesterol and cholesteryl ester concentrations in embryos obtained from diabetic rats during early organogenesis, although no leptin effects on lipid concentrations were observed in control embryos at this developmental stage. In embryos obtained on day 13.5 of gestation leptin additions reduced cholesteryl ester concentrations in controls, and diminished cholesteryl ester, triglycerides and phospholipids in embryos from diabetic rats. We demonstrated that leptin plays a role in the regulation of NO concentrations and lipid homeostasis during embryo organogenesis and that the diabetic environment causes a reduction of leptin concentrations in rat embryos.