Introduction: Maternal deprivation (MD) during neonatal life has diverse long-term effects, including modification of metabolism. Some of these effects are sexually dimorphic. We have previously reported that MD in rats blocks the physiological neonatal leptin surge, which could underlie the long-term metabolic changes.
Hypothesis: We hypothesized that replacement of leptin during MD would normalize long-term endocrine changes.
Methods: MD was carried-out in Wistar rats for 24 h on postnatal day (PND)9. Female and male MD and control rats were treated from PND 9 to 13 with rat leptin (3 mg/kg per day s.c.) or vehicle. After weaning weight gain, food intake and pubertal onset were monitored and an oral glucose tolerance test (OGTT) performed at PND60. Rats were sacrificed at PND90. Serum insulin, leptin, interleukin 6 (IL6), and tumor necrosis factor (TNF)α levels were measured by multiplex assay.
Results: MD reduced weight gain (P<0.001) and food intake (P<0.005) and leptin treatment further decreased both parameters in males, with no effect in females. Leptin treatment delayed vaginal opening (pubertal onset) in females (P<0.05). In males MD (P<0.01) advanced pubertal onset. Leptin also advanced puberty in controls, but normalized it in MD males (P<0.005). The OGTT area under the curve was lower in females (P<0.001) compared to males and MD reduced it in both sexes (P<0.05), with no effect of leptin treatment. There was no effect of MD or leptin treatment on serum leptin, IL6, or TNFα levels. In males MD increased insulin levels, with neonatal leptin treatment normalizing it in MD rats, but increasing it in controls (P<0.05). No effect was found in females.
Conclusion: Neonatal leptin treatment of MD rats normalizes some of the endocrine parameters disrupted by this manipulation, but exacerbates other changes. Hence, the factors inducing long-term changes are most likely multiple with diverse interactions.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology