Leptin and the systems neuroscience of meal size control.

The development of effective pharmacotherapy for obesity will benefit from a more complete understanding of the neural pathways and the neurochemical signals whose actions result in the reduction of the size of meals. This review examines the neural control of meal size and the integration of two principal sources of that control--satiation signals arising from the gastrointestinal tract and CNS leptin signaling. Four types of integrations that are central to the control of meal size are described and each involves the neurons of the nucleus tractus solitarius (NTS) in the dorsal hindbrain. Data discussed show that NTS neurons integrate information arising from: (1) ascending GI-derived vagal afferent projections, (2) descending neuropeptidergic projections from leptin-activated arcuate and paraventricular nucleus neurons, (3) leptin signaling in NTS neurons themselves and (4) melanocortinergic projections from NTS and hypothalamic POMC neurons to NTS neurons and melanocortinergic modulation of vagal afferent nerve terminals that are presynaptic to NTS neurons.