A Gut Sense for Dietary Amino Acids

Abstract

To survive, animals must consume meals containing both calories for energy and amino acids to assemble molecular proteins. Extensive research has uncovered how visceral cues act in concert with peripheral nerves and central circuits to regulate energy intake. However, regulation of amino acid consumption has remained elusive. Because amino acids are structurally and biochemically diverse, how they are detected in a concerted fashion within the body is poorly understood. Here I show that sensory cells of the small intestine, the site where dietary amino acids are first made available, detect the essential amino acid lysine using the cationic amino acid transporter CAT-1. The preference for amino acids that follows two days of amino acid depletion relies on the intracellular kinase GCN2. In vitro depletion of amino acids enhances the sensitivity of STC-1 cells, an intestinal sensory epithelial cell line, to the essential amino acids lysine and leucine. Furthermore, knockdown of CAT-1, a downstream target of GCN2, in STC-1 cells decreases the sensitivity of these cells to the essential amino acid lysine. These results suggest that gut sensory cells utilize CAT-1 to detect the essential amino acid lysine, likely contributing to the detection of lysine within diets. These findings will promote future studies to uncover how an animal prioritizes specific amino acids during times of nutrient deficit. Moreover, it creates the possibility to evaluate how plasticity in our gut can direct appetitive decisions.