The functional role of the T1R family of receptors in sweet taste and feeding

Abstract

The discovery of the T1R family of Class C G protein-coupled receptors in the peripheral gustatory system a decade ago has been a tremendous advance for taste research, and its conceptual reach has extended to other organ systems. There are three proteins in the family, T1R1, T1R2, and T1R3, encoded by their respective genes, Tas1r1, Tas1r2, and Tas1r3. T1R2 combines with T1R3 to form a heterodimer that binds with sugars and other sweeteners. T1R3 also combines with T1R1 to form a heterodimer that binds with L-amino acids. These proteins are expressed not only in taste bud cells, but one or more of these T1Rs have also been identified in the nasal epithelium, gut, pancreas, liver, kidney, testes and brain in various mammalian species. Here we review current perspectives regarding the functional role of these receptors, concentrating on sweet taste and feeding. We also discuss behavioral findings suggesting that a glucose polymer mixture, Polycose, which rodents avidly prefer, appears to activate a receptor that does not depend on the combined expression of T1R2 and T1R3. In addition, although the T1Rs have been implicated as playing a role in glucose sensing, T1R2 knock-out (KO) and T1R3 KO mice display normal chow and fluid intake as well as normal body weight compared with same-sex littermate wild type (WT) controls. Moreover, regardless of whether they are fasted or not, these KO mice do not differ from their WT counterparts in their Polycose intake across a broad range of concentrations in 30-min intake tests. The functional implications of these results and those in the literature are considered.

Role of gut nutrient sensing in stimulating appetite and conditioning food preferences

“…In many mammalian species, sugars are detected by the heterodimeric T1R2ϩT1R3 sweet receptor located in taste cells on the tongue and palate (22,247). The same receptor responds to nonnutritive sweeteners and to some proteins and amino acids.…”

GPR40 and GPR120 fatty acid sensors are critical for postoral but not oral mediation of fat preferences in the mouse

“…The discovery that the same taste/nutrient receptors found in the mouth also exist in the gut has prompted renewed interest in the role of these receptors in the control of appetite and food intake (e.g., 2,8,10,13,14,34,36). The general view has been that nutrient sensing in the mouth promotes appetite, whereas gut sensing is responsible for inhibiting appetite by activating satiating/satiety circuits (30).…”

Taste cell-expressed α-glucosidase enzymes contribute to gustatory responses to disaccharides

“…gustation | sensory transduction | disaccharides | sucrase-isomaltase | maltase-glucoamylase I n humans, the heteromeric combination of type 1 taste receptors 2 and 3 (T1R2+T1R3, encoded by TAS1R2 and TAS1R3) forms a sweet taste receptor responsive to sugars (e.g., glucose, fructose, sucrose), noncaloric sweeteners (e.g., aspartame, sucralose, saccharin, acesulfame K, rebaudioside A), and protein sweeteners (e.g., monellin, thaumatin, and brazzein), but not polysaccharides (1). The mouse sweet receptor (T1R2+T1R3) also responds to sugars, some of the same noncaloric sweeteners (e.g., sucralose, saccharin, acesulfame K, rebaudioside A), but not the protein sweeteners or polysaccharides.…”