Blockage of the neonatal leptin surge affects the gene expression of growth factors, glial proteins and neuropeptides involved in the control of metabolism and reproduction in peri-pubertal male and female rats

Abstract

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.