T1R2/T1R3 polymorphism affects sweet and fat perception: Correlation between SNP and BMI in the context of obesity development.

Genetic variations in taste receptors are associated with gustatory perception and obesity, which in turn affects dietary preferences. Given the increasing tendency of people with obesity choosing sweet, high-fat meals, the current study assessed the cross-regulation of two polymorphisms of the sweet taste receptor (T1R2/T1R3), rs35874116 and rs307355, on fat sensitivity in Indian adults. We investigated the association between taste sensitivity and BMI in the T1R2, T1R3, and CD36 polymorphic and non-polymorphic groups. The general labelled magnitude scale (gLMS) was used to assess the taste sensitivity of 249 participants in addition to anthropometric data. TaqMan Probe-based RT-PCR was employed to determine the polymorphisms. Additionally, the colorimetric method utilizing 3, 5-dinitro salicylic acid was used to evaluate the participants' salivary amylase activity. The mean detection thresholds for linoleic acid (LA) and sucrose were greater in individuals with obesity (i.e., 0.97 ± 0.08 mM and 0.22 ± 0.02 M, respectively) than in healthy adults (p < 0.0001), indicating lower sensitivity. Moreover, it was found that a greater proportion of persons with obesity fall into the polymorphic groups (i.e., 52% with genotype CD36 AA, 44% with genotype T1R2 CC, and 40% with genotype T1R3 TT). All three single nucleotide polymorphisms support the Hardy-Weinberg equilibrium (p = 0.78). The Pearson correlation analysis between LA and the sucrose detection threshold revealed a significant (p < 0.0001) positive relationship with an r value of 0.5299. Moreover, salivary amylase activity was significantly (p < 0.05) higher in the polymorphic sub-groups. The results of our study imply that genetic variations in T1R2/T1R3 receptors affect perception of both sweetness and fat, which may have an effect on obesity.

Ponnusamy V ，Subramanian G ，Vasanthakumar K ，Muthuswamy K ，Panneerselvan P ，Krishnan V ，Subramaniam S ... -  《-》

Genetic variation in sweet taste receptors and a mechanistic perspective on sweet and fat taste sensation in the context of obesity.

Taste sensation enables humans to make nutritionally important decisions such as food preference and consumption. It functions as deterministic factors for unpropitious eating behavior, leading to overweight and obesity. The hedonistic feeling on consumption of fat and sugar-rich meals, in particular, has a negative influence on health. In addition, impairment in the taste receptors alters the downstream signaling of taste transduction pathway. Hence, genetic polymorphism in typical taste receptors is a predictor of taste sensitivity variance across individuals. The present review summarizes the effect of a single nucleotide polymorphism (SNP) in sweet taste receptors (T1R2/T1R3) on taste perception among individuals of various body mass index (BMI). Furthermore, in the context of obesity, we discussed the possibility of crosstalk between fat and sweet receptors as well as taste dysfunction in diseased individuals. In overall, a greater understanding of the physiological relationship between taste receptors, altered taste sensitivity, and genetic polymorphisms should lead to more effective obesity prevention approaches.

Ponnusamy V ，Subramanian G ，Muthuswamy K ，Shanmugamprema D ，Krishnan V ，Velusamy T ，Subramaniam S ... -  《-》

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 《-》

Salivary leptin and TAS1R2/TAS1R3 polymorphisms are related to sweet taste sensitivity and carbohydrate intake from a buffet meal in healthy young adults.

Han P ，Keast RSJ ，Roura E 《-》

Sensitivity of human sweet taste receptor subunits T1R2 and T1R3 to activation by glucose enantiomers.

We have previously shown that l-glucose, the non-caloric enantiomer of d-glucose, activates the human sweet taste receptor T1R2/T1R3 transiently expressed in HEK293T cells. Here, we show that d- and l-glucose can also activate T1R2 and T1R3 expressed without the counterpart monomer. Serine mutation to alanine in residue 147 in the binding site of T1R3 VFT domain, completely abolishes T1R3S147A activation by either l- or d-glucose, while T1R2/T1R3S147A responds in the same way as T1R2 expressed without its counterpart. We further show that the original T1R2 reference sequence (NM_152232.1) is less sensitive by almost an order of magnitude than the reference sequence at the time this study was performed (NM_152232.4). We find that out of the four differing positions, it is the R317G in the VFT domain of T1R2, that is responsible for this effect in vitro. It is significant for both practical assay sensitivity and because glycine is found in this position in ~20% of the world population. While the effects of the mutations and the partial transfections were similar for d and l enantiomers, their dose-response curves remained distinct, with l-glucose reaching an early plateau.

Dubovski N ，Ben-Shoshan Galeczki Y ，Malach E ，Niv MY ... -  《-》