The responses of hypothalamic NPY and OBRb mRNA expression to food deprivation develop during the neonatal‐prepubertal period and exhibit gender differences in rats

Abstract

Neuropeptide Y (NPY) is an important hypothalamic orexigenic neuropeptide that acts in the brain. It has been established that the fasting-induced up-regulation of NPY expression is mainly caused by a reduction in the activity of leptin, which is a hormone secreted by adipose tissue. We have reported that in female rats hypothalamic NPY mRNA expression does not respond to fasting during the early neonatal period, but subsequently becomes sensitive to it later in the neonatal period. In this study, we compared the developmental changes in the responses of NPY and leptin expression to fasting between male and female rats during the neonatal to pre-pubertal period. Fasting was induced by maternal deprivation during the pre-weaning period (postnatal days 10 and 20) and by food deprivation during the post-weaning period (postnatal day 30). Hypothalamic NPY mRNA expression was not affected by fasting on postnatal day 10, whereas it was increased by fasting on postnatal day 20 and 30 in both males and females. On the other hand, the serum leptin level was decreased by fasting at all examined ages in both sexes. Namely, hypothalamic NPY mRNA expression was not correlated with the reduction in the serum leptin level at postnatal day 10 in either sex. Under the fasted conditions, the hypothalamic NPY mRNA levels of the males were higher than those of the females on postnatal days 20 and 30, whereas no such differences were observed under the normal nourishment conditions. The serum leptin levels observed under the fasted conditions did not differ between males and females at any examined age. These results suggest that some hypothalamic NPY functions develop during the neonatal period and that there is no major difference between the sexes with regard to the time when NPY neurons become sensitive to fasting. They also indicate that hypothalamic NPY expression is more sensitive to under-nutrition in male rats than in female rats, at least during the pre-pubertal period.

Developmental changes in the hypothalamic mRNA levels of prepro‐orexin and orexin receptors and their sensitivity to fasting in male and female rats

“…In addition, although the response of pp‐orexin (Hcrt) mRNA expression to maternal deprivation in the neonatal period has been evaluated in one study (Yamamoto et al, 2000), the response of pp‐orexin/Hcrt mRNA expression to fasting during the prepubertal period and the responses of OX1R and OX2R mRNA expression to fasting have not been examined. We have reported that the developmental patterns of some hypothalamic factors differ slightly between the sexes (Matsuzaki et al, 2015a,b). In addition, it has been reported that some neuronal factors have low sensitivities to undernutrition in prenatal and/or early neonatal period and that nutritional conditions in such period give long‐lasting effects on the development and functions of these factors (Delahaye et al, 2008).…”

Developmental changes in hypothalamic SF-1, POMC, and ERα mRNA expression and their sensitivity to fasting in male and female rats

“…Although we could not clarify the mechanism by which ERα and POMC mRNA expression levels are maintained in females, some unidentified factors might be involved in the discrepancies between the responses seen in each sex. In addition, we evaluated the effects of fasting on serum leptin levels using similar experimental models in a previous rat study [6]. As a result, we found that although the serum leptin levels of both sexes were reduced by 24 h fasting at all examined ages (postnatal days 10, 20, and 30), no differences between the serum leptin levels of males and females were detected under the fed or fasting conditions.…”

“…We previously found that the basal levels of central and peripheral metabolic and nutritional regulatory factors change, and their responses to metabolic status develop, during the neonatal to pre-pubertal period [5,6]. Interestingly, the developmental changes in the expression levels of some factors and their responses to a negative energy status differ between males and females [5,6].…”

“…Interestingly, the developmental changes in the expression levels of some factors and their responses to a negative energy status differ between males and females [5,6]. It is speculated that differences in the gonadal hormonal milieu and the expression levels of gonadal receptors might be involved in the sexual dimorphism observed in the neonatal to pre-pubertal period.…”

Effects of Leptin on Na+/Ca2+ Exchanger in PC12 Cells

“…The house-keeping gene Tbp (TATA binding protein) was amplified to standardize the amount of sample RNA. Relative quantification of gene expression was achieved using the ΔCT method as described [34].…”