The role of the vagus nerve in metabolic regulation. Gastrointestinal and hepatic vagus nerve afferents (red) communicate alterations in peripheral levels of micronutrients and metabolic molecules to the brain. Neural interaction between the interconnected NTS, DMN and A P, within the dorsal vagal complex, and reciprocal projections between this brainstem region and several hypothalamic areas (arcuate and paraventricular nuclei and mediobasal and lateral areas), underlie brain integration of visceral information and the modulation of efferent motor vagus nerve output, leading to regulation of metabolic homeostasis. Efferent vagus nerve signalling (blue) can be triggered by sensing metabolic alterations in the brainstem and the hypothalamus. Complex communication between hypothalamic nuclei and other forebrain structures (such as the insula and premotor cortex, amygdala, nucleus accumbens, parabrachial nucleus and thalamus) mediate hedonic, motivational and rewarding aspects of feeding behaviour and their interaction with vagus nerve-mediated homeostatic mechanisms. Abbreviations: A P, area postrema; CCK, cholecystokinin; DMN, dorsal motor nucleus of the vagus nerve; GLP-1, glucagon-like peptide-1; NA, nucleus ambiguus; NTS, nucleus tractus solitarius; PYY, peptide YY.