Research Article: Clofibrate inhibits the umami-savory taste of glutamate

Date Published: March 1, 2017

Publisher: Public Library of Science

Author(s): Matthew Kochem, Paul A. S. Breslin, Hiroaki Matsunami.


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.

Partial Text

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. Umami taste is hypothesized to have evolved to guide the ingestion of foods rich in these compounds, including certain vegetables and meats, as well as any fermented, aged, or cooked foods [1]. Recently, umami and sweet taste receptors have been implicated as regulators of metabolic physiology as well [2].

These data show that clofibric acid inhibits in a dose dependent manner the umami taste intensity of 20 mM glutamate (Fig 1). In addition, clofibric acid inhibited umami intensity from glutamate prepared with GMP, but not IMP (Fig 2). Collectively, these data suggest that clofibric acid, which binds T1R3 in vitro, is a potent umami taste inhibitor in vivo, presumably via inhibition of the T1R3 subunit of the T1R1-T1R3 receptor. An in vitro study of T1R2-T1R3 by Maillet and colleagues showed that both lactisole and clofibric acid bind the transmembrane domain of T1R3 [16]. Thus, it appears that both lactisole and clofibrate inhibit the umami taste from glutamate by binding with similar affinities to T1R1-T1R3. The observation that high concentrations of clofibric acid completely inhibited umami taste in five subjects (Fig 1 inset), suggests that T1R1-T1R3 is the predominant elicitor of umami taste in humans. Although we cannot rule out at this time the inhibition of other candidate umami taste receptors, mGluR1, mGluR4, or NMDA, by clofibric acid.