Figure 1. Key central neural circuits in the regulation of energy balance.

a. Neural circuits mediating the effect of melanocortin on food intake and energy expenditure. POMC neurons and AgRP neurons in the ARH regulate food intake through stimulating or inhibiting LPBN-projecting MC4R-expressing neurons in the PVH, respectively. POMC neurons that project to the spinal cord stimulate adaptive thermogenesis in brown adipose tissues through the MC4R in sympathetic preganglionic neurons located in the IML.

b. Neural circuits mediating the effect of leptin on food intake and energy expenditure. In addition to POMC neurons and AgRP neurons, the ARH contains RIP-Cre neurons and NOS1 neurons. NOS1 neurons are also present in other brain areas. Leptin stimulates adaptive thermogenesis in brown adipose tissues by increasing GABA release of ARH Rip-Cre neurons onto NTS-projecting neurons in the ventral medial parvicellular part of the PVH (PVHmpv). Leptin simultaneously suppresses food intake by acting on NOS1 neurons in an undefined location.

c. Locations of BDNF neurons that sense nutritional state. Glucose and anorexigenic factors, such as leptin, CCK, and αMSH, stimulate Bdnf gene expression in the VMH and dorsal vagal complex that is comprised of the DMV and NTS, suggesting that BDNF neurons in these two brain areas are involved in the control of food intake. It remains to be elucidated how BDNF produced in these neurons regulates food intake.

Abbreviations: ARH, arcuate nucleus of the hypothalamus; DMH, dorsomedial hypothalamus; DMV, dorsal motor nucleus of the vagus; IML, intermediolateral column of the spinal cord; LPBN, lateral parabrachial nucleus; NTS, nucleus of the solitary tract; PVH, paraventricular hypothalamus; PVHa: anterior part of the PVH; PVHmpd, dorsal medial parvicellular part of the PVH; PVHmpv, ventral medial parvicellular part of the PVH; PVHp, posterior part of the PVH; VMH, ventromedial hypothalamus.