Postnatal intracerebroventricular exposure to leptin causes an altered adult female phenotype.
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.
Divisions 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.
Amit
A
Varma
Jing
J
He
Bo-Chul
BC
Shin
Lisa A
LA
Weissfeld
Sherin U
SU
Devaskar
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006728:Hormones / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism; D007276:Injections, Intraventricular; D020738:Leptin / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D009479:Neuropeptides / Q000378:metabolism; D009994:Osmolar Concentration; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D006728:Hormones; D020738:Leptin; D009479:Neuropeptides; D005947:Glucose