The effects of prenatal undernutrition and a high-fat postnatal diet on central and peripheral orexigenic and anorexigenic factors in female rats.

Prenatal undernutrition and postnatal overnutrition increase the risk of some peripheral and central metabolic disorders in adulthood. We speculated that disturbances of appetite/metabolic regulatory factors might already have been established in the early stages of life and contribute to obesity later in life. The effects of a high-fat diet on the levels of peripheral and central appetite/metabolic regulatory factors were compared between the offspring of normally nourished dams and those of undernourished dams in the peri-pubertal period. In the offspring of the normally nourished dams (control), the consumption of the high-fat diet resulted in lower hypothalamic mRNA levels of orexigenic factors (neuropeptide Y (NPY) and prepro-orexin (pporexin)), whereas no such changes were seen in the offspring of the undernourished dams (subjected to intrauterine growth restriction). These results indicate that in high-energy conditions either the adaptive response does not function properly or has not been established in the offspring of undernourished dams. Because NPY and pporexin are negatively regulated by leptin, these findings suggest that in the intrauterine growth restriction group, the leptin resistance of hypothalamic functions, which is usually caused by diet-induced obesity in adulthood, had already been established in the peri-pubertal period.