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Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype
Amit Varma1, Jing He, Bo-Chul Shin
1Divisions of Neonatology and Developmental Biology, Dept. of Pediatrics, David Geffen School of Medicine, University of California-Los Angeles, 10833 LeConte Ave., MDCC-B2-375, Los Angeles, CA 90095-1752, USA.
Insights
Neonatal intracerebroventricular leptin administration reduced body weight and altered feeding behavior. Postnatal leptin exposure impacts adult female metabolic profiles, suggesting lasting effects on leptin sensitivity.
Area of Science:
- Neuroendocrinology
- Metabolic Regulation
- Developmental Biology
Background:
- Leptin is a key hormone regulating energy homeostasis.
- Early-life hormonal exposures can have long-lasting effects on metabolism.
- Understanding leptin's developmental impact is crucial for metabolic health.
Purpose of the Study:
- To investigate the long-term effects of neonatal intracerebroventricular leptin administration.
- To examine the impact on hypothalamic neuropeptides, body weight, and metabolic profiles.
- To determine if early leptin exposure alters adult phenotype.
Main Methods:
- Daily intracerebroventricular leptin administration in neonatal rats (days 2-7).
- Assessment of hypothalamic neuropeptides (neuropeptide Y, alpha-MSH) and body weight.
- Analysis of metabolic and hormonal profiles (insulin, corticosterone, leptin, LH) in suckling and adult rats.
Main Results:
- Neonatal leptin caused a postnatal decline in body weight, persisting in adult females.
- Associated with reduced food intake and altered hypothalamic leptin receptor and neuropeptide Y.
- Adult females exhibited persistent hyperinsulinemia, hyperglycemia, and glucose intolerance.
Conclusions:
- Postnatal leptin administration significantly alters the adult female phenotype.
- This may be due to retained leptin sensitivity, potentially leading to a lipoatrophic state.
- Early-life leptin exposure has sex-specific long-term metabolic consequences.
Abstract:
We investigated the effect of daily intracerebroventricular (ICV) leptin administration (neonatal age 2-7 days) on hypothalamic neuropeptides (neuropeptide Y, alpha-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 mug.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 alpha-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.
