Clofibrate inhibits the umami-savory taste of glutamate.

Matthew Kochem,Paul A S Breslin,Hiroaki Matsunami

doi:10.1371/journal.pone.0172534

Matthew Kochem, Paul A S Breslin + Show 1 more

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https://doi.org/10.1371/journal.pone.0172534

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Abstract

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.

Highlights

Human umami taste perception is typically elicited by select amino acids, such as glutamate and aspartate, and certain 5’-ribonucleotides, such as inosine and guanosine
Expressed human T1R1-T1R3 is activated in vitro by L-glutamate and is enhanced by the 5’ ribonucleotides inosine monophosphate (IMP) and guanosine monophosphate (GMP) [6,10]. 5’ ribonucleotides are thought to bind a site near the T1R1 venus flytrap domain, thereby stabilizing the closed, activated conformation [11]
Clofibric acid inhibited umami intensity from glutamate prepared with GMP, but not IMP (Fig 2)

Summary

Introduction

Human umami (or savory) taste perception is typically elicited by select amino acids, such as glutamate and aspartate, and certain 5’-ribonucleotides, such as inosine and guanosine. In vitro functional expression data and mouse gene knock-out studies suggest that glutamate taste perception is transduced, in part, by the heteromeric G-protein coupled receptor (GPCR) T1r1-T1r3 and possibly by shortened splice variants of mGluR1 and mGluR4 receptors [3,4,5,6,7], as well as a variant of the N-methyl-D-Aspartate (NMDA) receptor [8,9]. Expressed human T1R1-T1R3 is activated in vitro by L-glutamate and is enhanced by the 5’ ribonucleotides inosine monophosphate (IMP) and guanosine monophosphate (GMP) [6,10]. Expressed human T1R1-T1R3 is activated in vitro by L-glutamate and is enhanced by the 5’ ribonucleotides inosine monophosphate (IMP) and guanosine monophosphate (GMP) [6,10]. 5’ ribonucleotides are thought to bind a site near the T1R1 venus flytrap domain, thereby stabilizing the closed, activated conformation [11]

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