Abstract P514: The Role Of Sweet And Umami Taste Receptors In The Heart

Abstract

The tongue can distinguish between five different tastes via the taste receptors, which are G-protein coupled receptors (GPCRs). There are two classes of taste receptors, the TAS1 (T1) and TAS2 (T2) families, and the T1R1-T1R3 dimer senses the umami taste and T1R2-T1R3 senses the sweet taste. Recently, the taste receptors have also been found in the brain, lungs, intestine and pancreas, where they sense changes in the nutrient environment and respond through GPCR signalling. Given the importance of glucose and amino acid metabolism in the heart, we hypothesized that the sweet and umami taste receptors have an important function in the heart. Using a variety of technologies and disease states, we have identified that T1R1, T1R2 and T1R3 are expressed in the heart. More specifically, mass spectrometry of a dog model of dyssynchrony has shown the presence of T1R1, T1R3 and T1R2. RNA seq of human patients who received a Left Ventricular Assist device and those who did not also revealed the presence of T1R1 and T1R3. The expression of these proteins was also confirmed using Western blot. We further showed T1R2 and T1R3 protein is localized in the plasma membrane of the cardiomyocytes by immunofluorescence (colocalized with Na/K ATPase) and PM enrichment. When we compared the taste receptor protein levels in dilated cardiomyopathy (DCM) compared to donor heart tissue, we found that T1R2 was overexpressed in DCM, showing that taste receptors may be important in nutrient sensing in disease. Furthermore, when neonatal rat ventricular myocytes were treated with sweet and umami agonists (aspartame for the sweet taste receptor and monosodium glutamate for the umami receptor), they had increased calcium transients as shown by an increase in peak calcium. Cardiomyocytes treated with aspartame also showed a decrease in time to relax. We hypothesize that in the heart, sweet and umami receptors induce positive inotropy upon a change in nutrient environment.