Figure 3. Vagal gut-brain circuits regulate the physiological responses to a meal.

A) Vagal afferent neurons innervating the GI tract mediate gastrointestinal secretion and motility through vago-vagal circuits on the brainstem encompassing the NTS, the DMV and the Amb. B) Vagal afferent neurons innervate the pancreas, intestine, and hepatic portal area, providing an anatomical pathway for glucose detection. Furthermore, GLP1R-expressing neurons in the nodose ganglia might regulate glucose metabolism in response to gastric distension. Information from VANs is communicated to the NTS, where it could regulate glucose metabolism via at least two pathways: a vago-vagal reflex that promotes insulin release, and a hypothalamic pathway that regulates hepatic glucose production through vagal and/or spinal (sympathetic) efferent systems. C) VANs may detect different signals in the GI tract such as intestinal lipids and gastric distension to regulate thermogenesis. Since the NTS projects to hypothalamic areas involved in BAT thermogenesis, this pathway is probably mediated through a hypothalamus-SNS-BAT axis. D) Vagal afferent neurons detect hypotonic stimuli in the gut and hypertonic in the hepatic portal area and communicate this information to the NTS. In turn, the NTS relays this information to the SFO to mediate drinking behavior. NTS, nucleus of the solitary tract; DMV, dorsal motor nucleus of the vagus; Amb, nucleus ambiguus; HYP, Hypothalamus; SNS, sympathetic nervous system; BAT, brown adipose tissue; SFO, subfornical organ; NPY, neuropeptide; GLP-1R, glucagon-like peptide 1 receptor. Created in https://BioRender.com