Figure 2.

Major leptin-regulated neural systems and their outputs. Shown is a schematic diagram of major leptin-regulate brain systems, in a ventral (from the bottom) view of the rodent brain. Although all structures are bilateral, they are shown on only 1 side of the brain for the sake of simplicity. Note that the ARC, NTS, and PVH are bilateral but straddle the midline. Three major roles for leptin include the control of food intake and energy expenditure (red pathways), glucose homeostasis (green pathways), and motivated behavior (blue pathways). In the hindbrain, leptin action on the NTS increases satiety; these NTS LepRb neurons make reciprocal connections with hypothalamic nuclei (ARC, DMH, and PVH) that control food intake. Leptin also acts directly on the ARC and DMH, which (in addition to their reciprocal connections with each other) share strong reciprocal connections with the major output nucleus of the hypothalamus, the PVH. Leptin acts on these circuits to reduce food intake and increase energy expenditure. Direct leptin action on the ARC and VMH contribute to the suppression of glucose production and the stimulation of glucose disposal. Leptin action on the PBN also contributes to glycemic control, by suppressing glucose production during the CRR; PBN LepRb neurons mediate this effect via projections to the VMH. Leptin acts on LepRb neurons in the LHA to control the mesolimbic DA system. Not only do LHA LepRb neurons project to the VTA but also they modulate the activity of LHA HCRT neurons that project to the VTA. Thus, LHA LepRb neurons control the VTA neurons that project to the NAc to modulate the activity of the mesolimbic DA system and motivated behavior.