Abstract
OBJECTIVES: To investigate whether administration of leptin to rats during pregnancy and lactation affects placental 11β-hydroxysteroid dehydrogenase (11β-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 11β-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.
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Acknowledgements
We thank Anita Roberts, Joan Bushnell, Claire Cornick, Steven Wang, Kelly Smith and Lynne Ramage for their excellent technical assistance with this study.
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Stocker, C., O'Dowd, J., Morton, N. et al. Modulation of susceptibility to weight gain and insulin resistance in low birthweight rats by treatment of their mothers with leptin during pregnancy and lactation. Int J Obes 28, 129–136 (2004). https://doi.org/10.1038/sj.ijo.0802476
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DOI: https://doi.org/10.1038/sj.ijo.0802476
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