Neuroendocrine and neurometabolic circuitry regulation of metabolic functions. Both afferent and efferent pathways regulate energy balance through hormones and direct neural circuits. Ghrelin, insulin and leptin are the primary hormones that mediate the sensation of satiety and hunger by activating various populations of neurons in different regions of the brain. Autonomic innervations of metabolic organs are also depicted. SNS efferent fibers control hepatic and adipocyte metabolic pathways. Vagal afferents and efferent continuously monitor and regulate systemic metabolism. Cellular metabolism, including the production and release of cytokines from the spleen, responds to the sympathetic and parasympathetic convergences in the celiac ganglion. Inset, the NPY/AgRP and POMC neurons in the ARC of the hypothalamus inversely respond to these hormones and modulate the activation of the PVN neurons that in turn regulate feeding behavior and metabolic functions. Deep brain stimulation of POMC neurons ameliorates symptoms of diabetes in rat models, and therefore may provide a therapeutic avenue for neuromodulatory treatment of metabolic diseases. Image courtesy of Anthony S. Baker and Courtney Fleming, The Ohio State University© 2019; produced with permission.