Lipid-Lowering Pharmaceutical Clofibrate Inhibits Human Sweet Taste.

T1R2-T1R3 is a heteromeric receptor that binds sugars, high potency sweeteners, and sweet taste blockers. In rodents, T1R2-T1R3 is largely responsible for transducing sweet taste perception. T1R2-T1R3 is also expressed in non-taste tissues, and a growing body of evidence suggests that it helps regulate glucose and lipid metabolism. It was previously shown that clofibric acid, a blood lipid-lowering drug, binds T1R2-T1R3 and inhibits its activity in vitro The purpose of this study was to determine whether clofibric acid inhibits sweetness perception in humans and is, therefore, a T1R2-T1R3 antagonist in vivo Fourteen participants rated the sweetness intensity of 4 sweeteners (sucrose, sucralose, Na cyclamate, acesulfame K) across a broad range of concentrations. Each sweetener was prepared in solution neat and in mixture with either clofibric acid or lactisole. Clofibric acid inhibited sweetness of every sweetener. Consistent with competitive binding, inhibition by clofibric acid was diminished with increasing sweetener concentration. This study provides in vivo evidence that the lipid-lowering drug clofibric acid inhibits sweetness perception and is, therefore, a T1R carbohydrate receptor inhibitor. Our results are consistent with previous in vitro findings. Given that T1R2-T1R3 may in part regulate glucose and lipid metabolism, future studies should investigate the metabolic effects of T1R inhibition.

Kochem M ，Breslin PA 《-》

Clofibrate inhibits the umami-savory taste of glutamate.

Kochem M ，Breslin PA 《PLoS One》

Functional characterization of the heterodimeric sweet taste receptor T1R2 and T1R3 from a New World monkey species (squirrel monkey) and its response to sweet-tasting proteins.

The family C G protein-coupled receptor (GPCR) T1R2 and T1R3 heterodimer functions as a broadly acting sweet taste receptor. Perception of sweet taste is a species-dependent physiological process. It has been widely reported that New World monkeys and rodents are not able to perceive some of the artificial sweeteners and sweet-tasting proteins that can be perceived by humans, apes, and Old World monkeys. Until now, only the sweet receptors of humans, mice and rats have been functionally characterized. Here we report characterization of the sweet taste receptor (T1R2/T1R3) from a species of New World primate, squirrel monkey. Our results show that the heterodimeric receptor of squirrel monkey does not respond to artificial sweeteners aspartame, neotame, cyclamate, saccharin and sweet-tasting protein monellin, but surprisingly, it does respond to thaumatin at high concentrations (>18 μM). This is the first report demonstrating that species of New World monkey can perceive some specific sweet-tasting proteins. Furthermore, the sweet receptor of squirrel monkey responses to the such sweeteners cannot be inhibited by the sweet inhibitor lactisole. We compared the response differences of the squirrel monkey and human receptors and found that the residues in T1R2 determine species-dependent sweet taste toward saccharin, while the residues in either T1R2 or T1R3 are responsible for the sweet taste difference between humans and squirrel monkeys toward monellin. Molecular models indicated that electrostatic properties of the receptors probably mediate the species-dependent response to sweet-tasting proteins.

Liu B ，Ha M ，Meng XY ，Khaleduzzaman M ，Zhang Z ，Li X ，Cui M ... -  《-》

Non-nutritive sweetener activation of the pig sweet taste receptor T1R2-T1R3 in vitro mirrors sweetener stimulation of the gut-expressed receptor in vivo.

The perception of sweet is mediated by the sweet taste receptor T1R2-T1R3 expressed in taste cells of the lingual epithelium. This receptor is also expressed in intestinal enteroendocrine cells and is required for sensing luminal sugars and sweeteners to regulate expression of intestinal Na+-glucose cotransporter 1 (SGLT1). There are some notable differences amongst species in the ability to detect certain non-nutritive (artificial) sweeteners. Amino acid substitutions and pseudogenization of taste receptor genes are responsible for these disparities. Using heterologous expression, we demonstrate that the commonly used non-nutritive sweeteners sucralose, saccharin and acesulfame K activate pig T1R2-T1R3, but that aspartame and cyclamate do not. Furthermore, we show that in vitro sweetener activation of pig T1R2-T1R3 mirrors the sweetener stimulation of the gut-expressed receptor in vivo. Considering that sweeteners are included in animal feed worldwide, determination of taste receptor specificities in different species is essential for the development of scientifically-based dietary formulations.

Daly K ，Moran AW ，Al-Rammahi M ，Weatherburn D ，Shirazi-Beechey SP ... -  《-》

Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors.

Simon BR ，Parlee SD ，Learman BS ，Mori H ，Scheller EL ，Cawthorn WP ，Ning X ，Gallagher K ，Tyrberg B ，Assadi-Porter FM ，Evans CR ，MacDougald OA ... -  《-》