Figure 8. Leptin is required to specify the normal balance of hormonal and viscerosensory information conveyed by AgRP and GLP-1 inputs that converge onto the PVH.

During development, the adipocyte-derived hormone leptin is secreted by adipose tissue and binds to leptin receptors (LepRb) located on AgRP neurons in the ARH, and on PPG neurons in the NTS. In animals with normal leptin signaling, the PVH contains a greater density of AgRP inputs compared with that of GLP-1. In the absence of leptin signaling, the density of AgRP inputs to the PVH decreases and those derived from PPG neurons in the NTS increase. Thus, in contrast to the growth-promoting actions of leptin on AgRP neurons, leptin appears to suppress innervation by PPG neurons to the PVH, through a receptor dependent and cell-autonomous mechanism. Leptin’s developmental actions may function to balance excitatory and inhibitory inputs that converge onto multiple populations of PVH neurons and regulate their responsiveness to environmental signals.