Modulatory effect of leptin on nitric oxide production and lipid metabolism in term placental tissues from control and streptozotocin-induced diabetic rats
Verónica White A , Elida González A , Evangelina Capobianco A , Carolina Pustovrh A , Carlos Soñez B , María Cristina Romanini B and Alicia Jawerbaum A C
+ Author Affiliations
- Author Affiliations
A Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Serrano 669, (1414) Buenos Aires, Argentina.
B Departamento de Anatomía Animal, Facultad de Agronomía y Veterinaria, Universidad Nacional de Río Cuarto, 5800 Córdoba, Argentina.
C To whom correspondence should be addressed. email: a.jawerbaum@abaconet.com.ar
Reproduction, Fertility and Development 16(3) 363-372 https://doi.org/10.1071/RD03095
Submitted: 20 October 2003 Accepted: 30 March 2004 Published: 25 May 2004
Abstract
Leptin production by placental tissues contributes to its circulating levels and functions. The diabetic pathology induces alterations in leptin levels. In the present study, leptin levels were evaluated in placental tissue from control and neonatal streptozotocin-induced (n-STZ) diabetic rats during late gestation. The effects of leptin levels on the generation of nitric oxide (NO), prostaglandin (PG) E2 production and lipid metabolism were examined. Leptin levels were diminished in placentas from n-STZ diabetic rats compared with controls (P < 0.01). These differences were also evident when leptin was evaluated immunohistochemically. Addition of leptin (1 nm) in vitro enhanced NO production in control (66%) and diabetic placentas (134%) by stimulating NO synthase activity (by 38% and 54%, respectively). The addition of leptin increased PGE2 production in placentas from control (173%) and diabetic rats (83%) and produced a 50% decrease in placental lipid levels (phospholipids, triacylglycerides, cholesterol and cholesteryl ester) without involving a reduction in de novo lipid synthesis. These data indicate that leptin enhances the production of placental NO and PGE2, vasoactive agents that modify placental blood flow, and that leptin stimulates placental lipid metabolism, probably generating more lipids for transfer to the fetus. In the diabetic rat, placental leptin was reduced, probably as a response to the maternal environment to locally regulate the transfer of nutrients to the developing fetus.
Extra keyword: diabetes in pregnancy.
Acknowledgment
This work has been supported by grants PIP 2529/99 (A. J.) and PIP 0598/98 (E. G.) from Consejo Nacional de Investigaciones Científicas y Técnicas, and by Agencia de Promoción Científica y Tecnológica de Argentina (PICT 03 05-10652 to E. G.). E. C. is supported by PROGRESAR Program, ICMER, Chile.
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