FIGURE C-2 Pictorial representation of potential action of gut peptides on the hypothalamus. Access circulating agents into the arcuate nucleus of the hypothalamus is facilitated by a relaxed blood-brain barrier. Primary neurons in the arcuate nucleus contain multiple peptide neuromodulators. Appetite-inhibiting neurons (red) contain pro-opiomelanocortin (POMC) peptides such as α-melanocyte-stimulating hormone (αMSH), which acts on melanocortin receptors (MC3 and MC4) and cocaine- and amphetamine-stimulated transcript peptide (CART), whose receptor is unknown. Appetite-stimulating neurons in the arcuate nucleus (green) contain neuropeptide Y (NPY), which acts on Y receptors (Y1 and Y5), and agouti-related peptide (AgRP), which is an antagonist of MC3/4 receptor activity. Integration of peripheral signals within the brain involves interplay between the hypothalamus and hindbrain structures including the NTS, which receives vagal afferent inputs. Inputs from the cortex, amygdala, and brainstem nuclei are integrated as well, with resultant effects on meal size and frequency, gut handling of ingested food, and energy expenditure. →, direct stimulatory; , direct inhibitory; , indirect pathways. SOURCE: [130].