1. Arcuate-LHA connections relevant to appetite control
Arcuate-LHA connections relevant to appetite control. Neurons that express the leptin receptor have been termed “first-order” neurons because they respond directly to leptin. These neurons exist in the arcuate nucleus of the hypothalamus, in the brainstem and elsewhere. Major populations of appetite stimulating (“orexigenic”) and appetite suppressing (“anorectic” or “anorexigenic”) neurons exert opposing activities downstream of leptin. One key group of orexigenic first-order neurons is those that coexpress neuropeptide Y and agouti-related peptide (AgRP). These are shown in green. Binding of leptin to its receptor on the cell surface suppresses the firing of these NPY/AgRP neurons and reduces the release of the orexigenic molecules NPY and AgRP (dark grey and light grey circles, respectively). AgRP competes with alpha-MSH (yellow circles) for binding to the MC4R protein (red serpentine molecule) on downstream “second-order” neurons concentrated in the lateral hypothalamic area. Alpha-MSH is cleaved from POMC, which is expressed in a separate sub population of first-order neurons (shown in yellow) that also respond to leptin. The POMC peptide (multicolored circles within the yellow neuron) is processed by proprotein convertase-1 (PCSK1—grey sphere) into numerous peptides, among them ACTH, endorphins and alpha-MSH (yellow circles). Second-order neurons express proteins like melanin-concentrating hormone (MCH—blue circles within blue neurons) and orexins/hypocretins (red circles within red neurons). Multicolored circles within the red neuron indicate preproorexin, multicolored circles within the blue neuron indicate prepromelanin-concentrating hormone. Numerous other receptors such as the ghrelin receptor (purple serpentine molecule), serotonin receptors (yellow serpentine molecule), NPY receptors (green serpentine molecules), and others (blue and grey serpentine molecules) are important to modulating the hunger/satiety signal at multiple other sites in the brain.
Source: Child and Adolescent Obesity, Pediatric Endocrinology and Inborn Errors of Metabolism, 2e
Citation: Sarafoglou K, Hoffmann GF, Roth KS. Pediatric Endocrinology and Inborn Errors of Metabolism, 2e; 2017 Available at: Accessed: November 11, 2017
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