Postnatal development of hypothalamic leptin receptors.

The hormone, leptin, plays a key role in the regulation of energy balance and neuroendocrine function, as well as modulating a range of other physiological systems from immunity to cognition. In the adult brain, leptin regulates food intake and energy expenditure primarily via the hypothalamus. In addition to these well-defined actions in adult life, there is increasing evidence for a role of leptin during development. Leptin receptors are widely expressed in the developing brain from an early stage, and leptin is known to have profound effects on the proliferation, maintenance, and differentiation of neuronal and glial cells. During the early postnatal period, in both rats and mice, there is a surge in circulating leptin concentrations. Despite this elevation in leptin, neonates maintain a high level of food intake, and both feeding behavior and metabolic responses to exogenous leptin administration are absent until around the time of weaning. However, it is during this period that direct neurotrophic actions of leptin have been demonstrated, with leptin promoting neurite outgrowth and the establishment of hypothalamic circuitry. Exactly how leptin exerts these effects remains unknown, but changes in the distribution of hypothalamic leptin receptors during this period may, at least in part, underlie these age-specific effects of leptin.