ESPE Abstracts (2014) 82 P-D-1-1-105

Being Overweight During the Peripubertal Period Modifies the Leptin Induced Changes in Hypothalamic Neuropeptides Involved in Metabolism but not those Involved in Pubertal Onset

David Castro-Gonzáleza,b, Esther Fuente-Martína,b, Miguel A Sánchez-Garridob,c, Pilar Argente-Arizóna,b, Manuel Tena-Sempereb,c, Julie A Chowena,b & Jesús Argentea,b

aDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Department of Pediatrics, Universidad Autonoma de Madrid, Madrid, Spain; bCIBERobn Instituto Carlos III, Madrid, Spain; cUniversidad de Córdoba, IMIBIC/HURS, Córdoba, Spain

Background: Leptin is suggested to be a permissive factor in the onset of puberty by signaling at the level of the hypothalamus to indicate adequate energy stores. Overweight female rats due to increased neonatal nutrition have been shown to develop puberty before normal weight rats.

Objective and hypothesis: We hypothesized that this permissive effect may be due not only to increased leptin levels, but also to increased hypothalamic sensitivity to this hormone before pubertal onset.

Methods: On the day of birth Wistar rats were arranged into litters of four (neonatal overnutrition (NO)) or 12 (control (Ct)) pups and weaned on postnatal day (PND) 21. On PND30 all rats remained prepubertal although NO rats weighed more than Ct rats and had higher serum leptin levels. They then received an i.p. injection of leptin (3 μg/g bodyweight) or vehicle and were sacrificed 2 h later.

Results: Both Ct and NO rats had a rise in hypothalamic phosphorylated STAT3 levels, but this rise was significantly greater in NO rats (P<0.05). Basal hypothalamic neuropeptide Y mRNA levels were higher in NO rats, with levels in both Ct and NO rats decreasing in response to leptin, with a greater decline in NO rats (P<0.05). Proopiomelanocortin mRNA levels were not different at baseline, but the leptin induced rise was significantly greater in NO rats (P<0.01). There were no baseline differences between Ct and NO rats in GnRH, Kisspeptin, or Kiss receptor mRNA levels and leptin had no significant effect in either group.

Conclusion: There is an increased response of metabolic neuropeptide systems in overweight peripubertal female rats to an acute rise in leptin levels. However, leptin induced no changes in reproductive neuropeptides in control or overweight rats. Thus, during the peripubertal period the response of hypothalamic neuronal systems may be differentially affected by changes in leptin.