Differential leptin access into the brain--a hierarchical organization of hypothalamic leptin target sites?

Leptin target sites are found in several hypothalamic areas with dense populations of long form leptin receptor (LepRb) expressing neurons which mediate important leptin actions. Leptin action has been most intensely investigated in the arcuate nucleus of the hypothalamus (ARC), which represents an important leptin target site. Recent data have shown that non-ARC leptin target sites mediate important aspects of leptin action, however, including the regulation of energy balance. Therefore, the investigation of discrete leptin signaling systems and their interactions will be an important step to understand the homeostatic action of leptin. In this review I discuss our recent data investigating important differences in leptin accessibility to ARC neurons in contrast to other hypothalamic sites like the dorsomedial hypothalamus (DMH) and discuss their importance for the leptin signaling system.