Pre-pubertal serum leptin levels and sensitivity to central leptin injection of prenatally undernourished female rats.

It has been reported that intrauterine undernutrition is closely associated with the pathogeneses of certain diseases in adulthood; i.e., insulin resistance and diabetes, and that leptin resistance plays a pivotal role in the pathology of such intrauterine growth restriction (IUGR)-related conditions. Therefore, examinations of IUGR-induced leptin resistance in early developmental period are important for protecting against future disease. In this study, the effects of prenatal undernutrition on the serum leptin levels and central leptin responses of rats during the neonatal and/or pre-pubertal period were examined. The 50% food-restricted undernourished dams' offspring (UNO) exhibited a significantly lower birth weight than the normal nutrition dams' offspring (NNO). However, the UNO grew rapidly, and their mean body weight had caught up with that of the NNO by postnatal day 8. Thus, there were no significant differences between the body weights of the two groups at postnatal day 12, 16, 20, or 28. The serum leptin levels of the UNO were significantly higher than those of the NNO at postnatal days 20 and 28. At postnatal day 28, no significant difference in the hypothalamic mRNA level of neuropeptide Y, which is the main target of leptin, or that of ObRb, which is the leptin receptor, was detected between the NNO and UNO. The chronic intracerebroventricular injection of leptin attenuated body weight gain in both the NNO and UNO; however, there were no significant differences between the body weights of the two groups at any of the examined postnatal time points, indicating that the UNO and NNO exhibited similar central sensitivity to leptin during the pre-pubertal period. These results suggest that prenatal undernutrition induces leptin resistance until the neonatal to pre-pubertal period and that these alterations might be caused by impaired transportation of leptin to central tissues.