Development of leptin-sensitive circuits

Energy homeostasis is achieved by the integration of peripheral metabolic signals by neural circuits. The organisation and function of neural circuits regulating energy homeostasis has been the subject of intense investigation and has led to the definition of a core circuitry in the hypothalamus that interacts with key regions in the brain stem, which appear to mediate many of the effects of the adipocyte-derived hormone leptin on feeding and energy balance. Recent data on the ontogeny of these pathways indicate that, in rodents, these feeding circuits primarily form during neonatal life and remain structurally and functionally immature until 3 weeks of life. Our understanding of the mechanisms promoting the formation of these critical circuits has been advanced significantly by recent evidence showing that neonatal leptin acts as a neurotrophic factor promoting the development of projections from the arcuate nucleus of the hypothalamus. Together with an expanding literature on the role of nutritional factors to affect health, these discoveries may contribute to our understanding on perinatally acquired predisposition to later disease, such as obesity and diabetes.