Adaptation of liver to the postprandial state requires coordinated regulation of protein synthesis and folding aligned with changes in lipid metabolism. Here we demonstrate that sensory food perception is sufficient to elicit early activation of hepatic mTOR signaling, Xbp1 splicing, increased expression of ER-stress genes, and phosphatidylcholine synthesis, which translate into a rapid morphological ER remodeling. These responses overlap with those activated during refeeding, where they are maintained and constantly increased upon nutrient supply. Sensory food perception activates POMC neurons in the hypothalamus, optogenetic activation of POMC neurons activates hepatic mTOR signaling and Xbp1 splicing, whereas lack of MC4R expression attenuates these responses to sensory food perception. Chemogenetic POMC-neuron activation promotes sympathetic nerve activity (SNA) subserving the liver, and norepinephrine evokes the same responses in hepatocytes in vitro and in liver in vivo as observed upon sensory food perception. Collectively, our experiments unravel that sensory food perception coordinately primes postprandial liver ER adaption through a melanocortin-SNA-mTOR-Xbp1s axis. Display omitted Display omitted •Food perception activates hepatic mTOR and Xbp1 signaling•Food perception promotes changes in hepatic phosphatidylcholine synthesis•POMC neurons rapidly respond to food perception and control SNA to liver•Norepinephrine signaling in liver stimulates mTOR and Xbp1 activation The sight and smell of food are sufficient to induce liver endoplasmic reticulum reprogramming through a hypothalamic circuit, thereby anticipating the metabolic changes required for nutrient intake.