1. ¹Clore Laboratory, University of Buckingham, Buckingham, UK
2. ²Endocrinology Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK

Correspondence: Dr MA Cawthorne, Clore Laboratory, University of Buckingham, Buckingham MK18 1EG, UK. E-mail: mike.cawthorne@buckingham.ac.uk

Received 7 April 2003; Revised 3 July 2003; Accepted 3 August 2003; Published online 14 October 2003.

Abstract

OBJECTIVES: To investigate whether administration of leptin to rats during pregnancy and lactation affects placental 11-hydroxysteroid dehydrogenase (11-HSD2) activity and the susceptibility of their offspring to weight gain and insulin resistance.

DESIGN: Pregnant rats fed on a low-protein diet were administered leptin or saline by subcutaneous minipump from day 14 of gestation and throughout lactation. A further group was fed a normal diet and given saline. After weaning, the offspring of each group were fed on a normal diet until 6 weeks of age and then half of each group was transferred to a high-fat diet until 12 months of age.

RESULTS: Plasma leptin levels were raised two-fold on days 16–18 of pregnancy in the leptin-treated dams, but, despite a constant rate of infusion, at parturition they dipped to control levels before rising again. The activity of placental 11-HSD2 was reduced by the low-protein diet; this reduction was prevented by treating the dams with leptin. The male offspring of the saline-treated dams gained more weight and had higher plasma leptin levels on the high fat than the chow diet, but the offspring of the leptin-treated dams did not. Fasting blood glucose and intraperitoneal glucose tolerance at 6 and 12 months of age was unaffected by the high-fat diet, but only the offspring of the leptin-treated dams achieved this control without raised insulin levels.

CONCLUSIONS: The rate of leptin clearance appears to increase at parturition. The administration of leptin to rats during late pregnancy and lactation makes their male offspring less susceptible to high-fat-diet-induced weight gain and insulin resistance.