Fig. 1

GLP-1 is secreted from enteroendocrine cells where it activates intestinal vagal afferents, located in the gut and portal circulation, further activating GLP-1-producing neurons in the nucleus tractus solitarii. These neurons project to several food-regulating areas, including the ventral tegmental area, the nucleus accumbens and the hypothalamus. There, GLP-1 directly activates POMC/CART neurons and indirectly inhibits, via GABAergic transmission, the NPY/AgRP neurons, which collectively results in signals reducing food intake. Efferent pathways, which originate in the brain stem, subsequently signal to peripheral organs to close the loop of feeding behavior and glucose metabolism regulation. GLP-1 receptors are also expressed on the choroid plexus epithelial cells, where the binding of GLP-1 reduces Na + K + ATPase activity, leading to decreased CSF secretion and consequently decreased ICP. Created with BioRender.com. AgRP: agouti-related peptide, AP: area postrema, CART: cocaine- and amphetamine-regulated transcript, CSF: cerebrospinal fluid, ENS: enteric nervous system, GLP-1: glucagon-like peptide-1, Hyp: hypothalamus, ICP: intracranial pressure, NPY: neuropeptide Y, NTS: nucleus tractus solitarii, POMC: proopiomelanocortin, SFO: subfornical organ