Changes in the responsiveness of serum leptin and hypothalamic neuropeptide Y mRNA levels to food deprivation in developing rats.

Neuropeptide Y (NPY) is an important orexigenic peptide that acts in the brain. The increase in hypothalamic NPY mRNA expression induced by fasting is mainly caused by a decrease in the effects of leptin. We investigated the developmental changes in the sensitivities of leptin and hypothalamic neuropeptide Y to fasting. Hypothalamic NPY mRNA levels were increased by fasting in postnatal days 15 and 25 rats, but not in postnatal day 5 rats. Serum leptin levels were decreased by fasting in rats at all ages (days 5, 15, and 25). In addition, hypothalamic OB-Rb mRNA levels were decreased by fasting in postnatal day 25 rats, but not in postnatal day 5 or 15 rats. Although the percentage of fating-induced decrease in the serum leptin level was larger in the postnatal day 15 rats than in the postnatal day 25 rats, the percentage of increase in the hypothalamic NPY mRNA level in the postnatal day 15 rats was smaller than that in the postnatal day 25 rats. There was a strong inverse correlation between serum leptin levels and hypothalamic NPY mRNA levels in the postnatal day 25 rats, whereas no significant correlation was found between these parameters in the postnatal day 5 or 15 rats. These findings indicate that the sensitivity of hypothalamic NPY mRNA expression to food deprivation and hypoleptinemia has developed by postnatal day 25.