title: Effects of acute changes in neonatal leptin levels on food intake and long-term metabolic profiles in rats.
abstract: In rodents there is a rise in serum leptin levels between postnatal days (PND) 5 and 14, with this neonatal leptin surge reported to modulate the maturation of hypothalamic circuits involved in appetite regulation. We hypothesized that acute changes in neonatal leptin levels have different long-term metabolic effects depending on how and when this surge is modified. To advance the timing of the normal leptin peak, male Wistar rats were injected with leptin (sc, 3 μg/g) on PND 2. To ablate the leptin peak on PND 10, a pegylated leptin antagonist (sc, 9 μg/g) was injected. Controls received vehicle. All rats were allowed to eat ad libitum until PND 150. Increased leptin on PND 2 reduced food intake (P<0.01) after 3 months of age with no effect on body weight. Levels of total ghrelin were reduced (P<0.001) and acylated ghrelin increased (P<0.05), with no other modifications in metabolic hormones. In contrast, treatment with the leptin antagonist on PND 9 did not affect food intake but reduced body weight beginning around PND 60 (P<0.02). This was associated with a reduction in fat mass, insulin (P<0.01), and leptin (P<0.007) levels and an increase in testosterone levels (P<0.01). Hypothalamic neuropeptide Y (P<0.05) and leptin receptor (P<0.005) mRNA levels were reduced, whereas mRNA levels for uncoupling protein 2 (P<0.005) were increased in visceral fat, which may indicate an increase in energy expenditure. In conclusion, acute changes in neonatal leptin levels induce different metabolic profiles depending on how and when leptin levels are modified.
authors.affiliation: Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, and Department of Pediatrics, Universidad Autónoma de Madrid, Avenida Menéndez Pelayo, 65, 28009 Madrid, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Granado
authors.forename: Cristina
authors.initials: C
authors.lastname: García-Cáceres
authors.forename: Esther
authors.initials: E
authors.lastname: Fuente-Martín
authors.forename: Francisca
authors.initials: F
authors.lastname: Díaz
authors.forename: Virginia
authors.initials: V
authors.lastname: Mela
authors.forename: Maria-Paz
authors.initials: MP
authors.lastname: Viveros
authors.forename: Jesús
authors.initials: J
authors.lastname: Argente
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chowen
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D054439:Ghrelin / Q000097:blood; D005951:Glucose Tolerance Test; D020738:Leptin / Q000031:analogs & derivatives / Q000097:blood* / Q000494:pharmacology; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D054411:Receptors, Leptin / Q000037:antagonists & inhibitors
chemical_list: D054439:Ghrelin; D020738:Leptin; D054411:Receptors, Leptin; C484843:pegylated leptin; D011092:Polyethylene Glycols