Clofibrate inhibits the umami-savory taste of glutamate

• Published in: PloS one Vol. 12; no. 3; p. e0172534
• Main Authors: Kochem, Matthew, Breslin, Paul A. S.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2017; Public Library of Science (PLoS)
• Subjects: Adult; Amino acids; Analysis; Biology and Life Sciences; Cardiovascular disease; Clofibrate; Clofibrate - administration & dosage; Clofibric acid; Diabetes; Digestive tract; Dosage and administration; Dose-Response Relationship, Drug; Drug metabolism; Drugs; Female; Food; G protein-coupled receptors; Gastrointestinal tract; Gene expression; Glucose; Glucose metabolism; Glutamate; Glutamic Acid - administration & dosage; Health aspects; Human subjects; Humans; In vivo methods and tests; Inhibition; Inosine monophosphate; Insulin; Lipid metabolism; Lipids; Male; Medicine and Health Sciences; Metabolism; Monosodium glutamate; Organs; Palatability; Perception; Physiology; Receptors; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - metabolism; Ribonucleotides; Rodents; Social Sciences; Sodium; Soft drinks; Taste; Taste buds; Taste perception; Taste Perception - drug effects; Taste receptors; Umami
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0172534

In humans, umami taste can increase the palatability of foods rich in the amino acids glutamate and aspartate and the 5'-ribonucleotides IMP and GMP. Umami taste is transduced, in part, by T1R1-T1R3, a heteromeric G-protein coupled receptor. Umami perception is inhibited by sodium lactisole, which binds to the T1R3 subunit in vitro. Lactisole is structurally similar to the fibrate drugs. Clofibric acid, a lipid lowering drug, also binds the T1R3 subunit in vitro. The purpose of this study was to determine whether clofibric acid inhibits the umami taste of glutamate in human subjects. Ten participants rated the umami taste intensity elicited by 20 mM monosodium glutamate (MSG) mixed with varying concentrations of clofibric acid (0 to 16 mM). In addition, fourteen participants rated the effect of 1.4 mM clofibric acid on umami enhancement by 5' ribonucleotides. Participants were instructed to rate perceived intensity using a general Labeled Magnitude Scale (gLMS). Each participant was tested in triplicate. Clofibric acid inhibited umami taste intensity from 20 mM MSG in a dose dependent manner. Whereas MSG neat elicited "moderate" umami taste intensity, the addition of 16 mM clofibric acid elicited only "weak" umami intensity on average, and in some subjects no umami taste was elicited. We further show that 1.4 mM clofibric acid suppressed umami enhancement from GMP, but not from IMP. This study provides in vivo evidence that clofibric acid inhibits glutamate taste perception, presumably via T1R1-T1R3 inhibition, and lends further evidence that the T1R1-T1R3 receptor is the principal umami receptor in humans. T1R receptors are expressed extra-orally throughout the alimentary tract and in regulatory organs and are known to influence glucose and lipid metabolism. Whether clofibric acid as a lipid-lowering drug affects human metabolism, in part, through T1R inhibition warrants further examination.