Physiological Significance of Glutamate Signaling in Gut-Brain Communication

Abstract

L-Glutamate is involved in the perception of umami taste, intermediary metabolism, and excitatory neurotransmission. In addition, recent studies have uncovered a variety of physiological roles for dietary glutamate, as evidenced by the fact that intragastric glutamate infusions induce flavor preference learning in rats. Moreover, glutamate increases digestive juice secretion and gastric emptying of protein-rich meals. Glutamate levels in blood and brain remain stable all day long even after the food intake since most of glutamate absorbed is oxidized in the mucosa of the small intestine as a primary energy source. Chronic ad libitum ingestion of glutamate solution contributes to reducing weight gain, fat deposition, and plasma leptin levels in comparison to ingestion of water. Glutamate receptors and their cellular transduction molecules have recently been identified in gut epithelial cells. Stimulation of gut glutamate receptors enhances the apical expression of glutamate transporters and also triggers the release of nitric oxide. Nitric oxide in its turn induces gut serotonin release, which increases vagal afferent inputs to different brain regions. Notably, three brain areas, i.e., the medial preoptic area, the dorsomedial nucleus of the hypothalamus, and the habenular nucleus are activated by intragastric glutamate infusions. Total subdiaphragmatic vagotomy abolishes this response. Consistent with the above, vagotomy specifically reduces the overall intake of glutamate. Taken together, these findings contribute to the growing body of evidence indicating that glutamate signaling via dedicated taste and gut receptors influences multiple physiological functions including gut secretion, motility, digestion, absorption, metabolism and energy homeostasis.