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Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype

²Divisions of Neonatology and Developmental Biology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California 90095; and Schools of ¹Medicine and ³Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15213

Submitted 28 May 2004 ; accepted in final form 12 August 2004

We investigated the effect of daily intracerebroventricular (ICV) leptin administration (neonatal age 2–7 days) on hypothalamic neuropeptides (neuropeptide Y, -melanocyte-stimulating hormone) that regulate food intake, body weight (BW) gain, and the metabolic/hormonal profile in suckling (8 and 21 days) and adult rat (35, 60, 90, and 120 days). ICV leptin (0.16 µg·g BW^–1·dose^–1; n = 70) led to a postnatal decline in BW (P = 0.0002) that persisted only in the adult females (P = 0.002). The postnatal decline in BW due to leptin was associated with a decline in food intake (P = 0.01) and hypothalamic leptin receptor (P = 0.008) and neuropeptide Y (P = 0.008) immunoreactivities and an increase in -melanocyte-stimulating hormone (P = 0.008) immunoreactivity. In addition, hyperinsulinemia (P = 0.01) with hypocorticosteronemia (P = 0.007) occurred during the postnatal period with hypercorticosteronemia (P = 0.007) and hypoleptinemia (P = 0.008) and an increase in leutinizing hormone (P = 0.01) in the adult male and female progeny. Persistent hyperinsulinemia (P = 0.015) with hyperglycemia (P = 0.008) and glucose intolerance (P = 0.001) were observed only in the adult female. We conclude that postnatal leptin administration alters the adult female phenotype and speculate that this may relate to retention of leptin sensitivity resulting in a lipoatrophic state.

development; ob gene; food intake; hyperinsulinemia; neuropeptide Y

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