RT Journal Article T1 Blockage of the neonatal leptin surge affects the gene expression of growth factors, glial proteins and neuropeptides involved in the control of metabolismand reproduction in peri-pubertal male and femalerats A1 Mela Rivas, Virginia A1 Díaz, Francisca A1 López Rodríguez, Ana Belén A1 Vázquez, María Jesús A1 Gertler, Arieh A1 Argente, Jesús A1 Tena-Sempere, Manuel A1 Viveros, María Paz A1 Chowen, Julie A. AB Leptin is important in the development of neuroendocrine circuits involved in metabolic control. As both leptin and metabolism influence pubertal development, we hypothesized that early changes in leptin signaling could also modulate hypothalamic systems involved in reproduction. We previously demonstrated that a single injection of a leptin antagonist on postnatal day (PND) 9, coincident with the neonatal leptin peak, induced sexually dimorphic modifications in trophic factors and markers of cell turnover and neuronal maturation in the hypothalamus on PND13. Here our aim was to investigate if the alterations induced by leptin antagonism persist into puberty. Accordingly, male and female rats were treated with a pegylated super leptin antagonist from PND5 to 9 and killed just before the normal appearance of external signs of puberty (PND 33 in females and PND 43 in males). There was no effect on body weight, but in males food intake increased, subcutaneous adipose tissue decreased and hypothalamic NPY and AgRP mRNA levels were reduced, with no effect in females. In both sexes, the antagonist increased hypothalamic mRNA levels of the kisspeptin receptor, Gpr54. Expression of the leptin receptor, trophic factors and glial markers were differently affected in the hypothalamus of peri-pubertal males and females. Leptin production in adipose tissue was decreased in antagonist treated rats of both sexes, with production of other cytokines being differentially regulated between sexes. In conclusion, in addition to the long-term effects on metabolism, changes in neonatal leptin levels modifies factors involved in reproduction that could possibly affect sexual maturation. PB Oxford University Press SN 0013-7227, ESSN: 1945-7170 YR 2015 FD 2015-07 LK https://hdl.handle.net/20.500.14352/23340 UL https://hdl.handle.net/20.500.14352/23340 LA eng NO Ministerio de Ciencia e Innovación (MICINN) NO Fondo de Investigación Sanitaria (España)-Fondo Europeo de Desarrollo Regional (FEDER) Program NO Universidad Complutense Madrid/Banco Santander Central Hispano NO Junta de Andalucía NO Redes Temáticas de Investigación Cooperativa en Salud (España) NO Instituto de Salud Carlos III-Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición (España) NO Fundación de Endocrinología y Nutrición (España) DS Docta Complutense RD 11 abr 2025