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BACKGROUND: Non‐nutritive sweeteners (such as sucralose) bind to sweet receptors Tas1r2/Tas1r3 on intestinal endocrine L cells after diets to upregulate blood glucose. However, the mechanism by which sucralose regulates postprandial blood glucose (PBG) has not been clarified to date. We hypothesized that the gut sweet taste receptor was one of the targets for sucralose to regulate PBG. The aim of this study was to examine the effect of sucralose on PBG based on the gut sweet taste receptor signaling pathway and to explore the mechanism. Therefore, we examined PBG, genes, and proteins associated with the gut sweet receptor pathway in sucralose‐exposed mice. RESULTS: The results showed that after 12 weeks of sucralose exposure the PBG of mice increased significantly, and the expression of intestinal sweet taste receptors increased correspondingly. Within the concentration range of this experiment, a significant increase of PBG was observed in mice fed on sucralose with a concentration equal to or higher than 0.33 g L−1. CONCLUSION: Long‐term consumption of sucralose may increase body weight and the risk of elevated PBG, resulting in overexpression of sweetness receptors and glucose transporters. The mechanism of these effects might be the result of non‐nutritive sweeteners binding to sweetness receptors Tas1r2/Tas1r3 in gut endocrine cells and upregulating Slc5a1 and Slc2a2. But we cannot rule out that the rise in PBG is the result of a combination of sweet receptors and gut microbes. Therefore, the effect of gut microbes on PBG needs to be studied further. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The innate immune system is crucial in fighting SARS-CoV-2 infection, which is responsible for coronavirus disease 2019 (COVID-19). Therefore, deepening our understanding of the underlying immune response mechanisms is fundamental for the development of novel therapeutic strategies. The role of extra-oral bitter (TAS2Rs) and sweet (TAS1Rs) taste receptors in immune response regulation has yet to be fully understood. However, a few studies have investigated the association between taste receptor genes and COVID-19 symptom severity, with controversial results. Therefore, this study aims to deepen the relationship between COVID-19 symptom presence/severity and TAS1R and TAS2R38 (TAS2Rs member) genetic variations in a cohort of 196 COVID-19 patients. Statistical analyses detected significant associations between rs307355 of the TAS1R3 gene and the following COVID-19-related symptoms: chest pain and shortness of breath. Specifically, homozygous C/C patients are exposed to an increased risk of manifesting severe forms of chest pain (OR 8.11, 95% CI 2.26–51.99) and shortness of breath (OR 4.83, 95% CI 1.71–17.32) in comparison with T/C carriers. Finally, no significant associations between the TAS2R38 haplotype and the presence/severity of COVID-19 symptoms were detected. This study, taking advantage of a clinically and genetically characterised cohort of COVID-19 patients, revealed TAS1R3 gene involvement in determining COVID-19 symptom severity independently of TAS2R38 activity, thus providing novel insights into the role of TAS1Rs in regulating the immune response to viral infections. [ABSTRACT FROM AUTHOR]

The innate immune system is crucial in fighting SARS-CoV-2 infection, which is responsible for coronavirus disease 2019 (COVID-19). Therefore, deepening our understanding of the underlying immune response mechanisms is fundamental for the development of novel therapeutic strategies. The role of extra-oral bitter (TAS2Rs) and sweet (TAS1Rs) taste receptors in immune response regulation has yet to be fully understood. However, a few studies have investigated the association between taste receptor genes and COVID-19 symptom severity, with controversial results. Therefore, this study aims to deepen the relationship between COVID-19 symptom presence/severity and TAS1R and TAS2R38 (TAS2Rs member) genetic variations in a cohort of 196 COVID-19 patients. Statistical analyses detected significant associations between rs307355 of the TAS1R3 gene and the following COVID-19-related symptoms: chest pain and shortness of breath. Specifically, homozygous C/C patients are exposed to an increased risk of manifesting severe forms of chest pain (OR 8.11, 95% CI 2.26–51.99) and shortness of breath (OR 4.83, 95% CI 1.71–17.32) in comparison with T/C carriers. Finally, no significant associations between the TAS2R38 haplotype and the presence/severity of COVID-19 symptoms were detected. This study, taking advantage of a clinically and genetically characterised cohort of COVID-19 patients, revealed TAS1R3 gene involvement in determining COVID-19 symptom severity independently of TAS2R38 activity, thus providing novel insights into the role of TAS1Rs in regulating the immune response to viral infections.

This study aims to investigate whether the trajectory of dental caries in the life course is associated with rs307355 (TAS1R3) and rs35874116 (TAS1R2) and if there is an epistatic association between rs307355 (TAS1R3) and rs35874116 (TAS1R2). A representative sample of all 5,914 births from the 1982 Pelotas birth cohort was prospectively investigated, and the decayed, missing, and filled teeth (DMF-T) components were assessed at ages 15 (n = 888), 24 (n = 720), and 31 (n = 539) y. Group-based trajectory modeling was used to identify groups with similar trajectories of DMF-T components in the life course. Genetic material was collected, and rs307355 (TAS1R3) and rs35874116 (TAS1R2) were genotyped. Ethnicity was evaluated using ADMIXTURE. Generalized multifactor dimensionality reduction software was used to investigate epistatic interactions. Considering rs307355 (TAS1R3) in the additive effect, the genotype TT was associated with the high decayed trajectory group (odds ratio [OR] = 4.52; 95% confidence interval [CI], 1.15–17.74) and the high missing trajectory group (OR = 3.35; 95% CI, 1.09–10.26). In the dominant effect, the genotype CT/TT was associated with the high decayed trajectory group (OR = 1.64; 95% CI, 1.14–2.35). Allele T was associated with an increased odds of 64% (OR = 1.64; 95% CI, 1.20–2.25) for the decayed component and 41% (OR = 1.41; 95% CI, 1.04–1.92) for the missing component. No associations were observed between rs307355 (TAS1R3) and the filled component. rs35874116 (TAS1R2) was not associated with DMF-T components. Positive epistatic interactions were observed involving rs307355 (TAS1R3) and rs35874116 (TAS1R2) with the decayed component (OR = 1.72; 95% CI, 1.04–2.84). Thus, rs307355 (TAS1R3) genotypes and alleles seem positively associated with the trajectory of decayed and missing components in the life course. Epistatic interaction between rs307355 and rs35874116 may increase the decayed caries trajectory. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of the study is to analyze the association of different bitter and sweet gene receptor polymorphisms and bitter and sweet food consumption on formation of dental caries in Turkish adult population.

Objective: It is known that genetic variations in the mechanism of taste perception play an essential role in food intake. In this study, we investigated the SNP rs35874116 polymorphism in the sweet taste receptor (TAS1R2) gene and nutrient intakes of adults. Methods: The study conducted with 95 volunteers. Food consumption records of participants obtained by 24-h recall method, and analyzed by Computer-Aided Nutrition Software, Nutrition Information Systems 8.1 Package Software (BeBiS). Venous blood samples of the participants were collected to determine genotype distribution, and genotype distributions were determined using the Kompetitive Allele-Specific PCR (KASP) method. Results: The genotype examination of participants revealed that the percentage of individuals with GA, AA, and GG genotypes were 67.3%, 26.3%, and 6.3% respectively. Daily total carbohydrate and sucrose intakes were found as the highest in individuals with GG genotype (145.55±56.69 g and 28.66±26 g, respectively), but without statistical difference. Conclusion: According to our knowledge the study is the first to examine TAS1R2 polymorphism and nutrient intake in the Turkish population. We did not find any difference between TAS1R2 (rs35874116) polymorphism and nutrient intake; however, the study may serve as a preliminary result. Studies with a wider sample may help to enhance our understanding of the TAS1R2 and nutrient intake. [ABSTRACT FROM AUTHOR]

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Objective: Sweet taste receptors (STR) are expressed in the gut and other extra-oral tissues, suggesting that STR-mediated nutrient sensing may contribute to human physiology beyond taste. A common variant (Ile191Val) in the TAS1R2 gene of STR is associated with nutritional and metabolic outcomes independent of changes in taste perception. It is unclear whether this polymorphism directly alters STR function and how it may contribute to metabolic regulation. Methods: We implemented a combination of in vitro biochemical approaches to decipher the effects of TAS1R2 polymorphism on STR function. Then, as proof-of-concept, we assessed its effects on glucose homeostasis in apparently healthy lean participants. Results: The Ile191Val variant causes a partial loss of function of TAS1R2 through reduced receptor availability in the plasma membrane. Val minor allele carriers have reduced glucose excursions during an OGTT, mirroring effects previously seen in mice with genetic loss of function of TAS1R2. These effects were not due to differences in beta-cell function or insulin sensitivity. Conclusions: Our pilot studies on a common TAS1R2 polymorphism suggest that STR sensory function in peripheral tissues, such as the intestine, may contribute to the regulation of metabolic control in humans.

The class C G protein‐coupled sweet taste receptor (STR) is responsible for the perception of sweet‐tasting molecules. Considered an obligate heterodimer, it consists of taste 1 receptor 2 and taste 1 receptor 3 subunits. Interest in the STR has steadily grown, especially since its discovery in extraoral tissues hints at a metabolic role for the receptor. It is now known that many pharmacologically exploitable binding sites exist across the extracellular and transmembrane regions of both subunits of the STR, indicative of its potential amenability to pharmacotherapeutic modulation. In this review, we briefly describe the structural characteristics and functional relevance of the STR. Then, from a molecular pharmacology perspective, we dissect the research surrounding the regulation of STR surface expression and signal transduction, in both oral and extraoral tissues, and discuss the potential for the exploitation of biased agonists for the STR. We find that despite 20 years of research into the STR, the target remains frustratingly enigmatic. Not only are the mechanisms controlling and regulating the surface expression of the STR unclear, but also research into the full repertoire of signaling partners of the STR is at present inconclusive. Critically, the influence of receptor polymorphisms (including those associated with sugar consumption) on the molecular pharmacology of the receptor remains hitherto unexplored. Finally, we provide recommendations on the reporting of reference sequence identification numbers to avoid incorrect attribution of wild‐type to these biologically significant polymorphisms, which we argue may have led to some of the inconsistencies in the field. [ABSTRACT FROM AUTHOR]

Sweet substances are detected by taste-bud cells upon binding to the sweet-taste receptor, a T1R2/T1R3 heterodimeric G protein-coupled receptor. In addition, experiments with mouse models lacking the sweet-taste receptor or its downstream signaling components led to the proposal of a parallel "alternative pathway" that may serve as metabolic sensor and energy regulator. Indeed, these mice showed residual nerve responses and behavioral attraction to sugars and oligosaccharides but not to artificial sweeteners. In analogy to pancreatic β cells, such alternative mechanism, to sense glucose in sweet-sensitive taste cells, might involve glucose transporters and KATP channels. Their activation may induce depolarization-dependent Ca2+ signals and release of GLP-1, which binds to its receptors on intragemmal nerve fibers. Via unknown neuronal and/or endocrine mechanisms, this pathway may contribute to both, behavioral attraction and/or induction of cephalic-phase insulin release upon oral sweet stimulation. Here, we critically review the evidence for a parallel sweet-sensitive pathway, involved signaling mechanisms, neural processing, interactions with endocrine hormonal mechanisms, and its sensitivity to different stimuli. Finally, we propose its physiological role in detecting the energy content of food and preparing for digestion. [ABSTRACT FROM AUTHOR]

The taste receptor type I (Tas1R) family consists of three G protein-coupled receptors (T1R1, T1R2, and T1R3) that form heterodimers recognizing sweet compounds (T1R2/T1R3) or amino acids (T1R1/T1R3). These receptors are nutrient sensors that facilitate appropriate physiological responses with nutrient availability. However, their contribution to the development of pathologies associated with overnutrition (e.g., atherosclerosis) is unclear. The aim of the present study was to determine if T1R3 deletion would reduce atherosclerotic plaque development in mice. We generated atherosclerotic mice with whole-body deletion of T1R3 by crossing T1R3−/− mice with ApoE−/− mice. T1R3+/+ ApoE−/− and T1R3−/− ApoE−/− mice were maintained on an atherogenic high-fat diet for 8 weeks. Weight gain and food consumption were measured during the 8-week diet. Atherosclerotic lesion development and size were assessed by en face analysis of intact aortas and microscopic analysis of aortic roots. Our results indicate that T1R3 deletion in male and female ApoE−/− mice reduces aortic atherosclerotic plaque accumulation. Hepatic triglyceride accumulation, which was measured by quantification of oil red O staining, was also reduced in T1R3−/− mice. While the ablation of T1R3 reduced the final body weight of both males and females by approximately 12%, serum lipids, insulin, and glucose were either unchanged or slightly reduced. Immunoblot analysis of the phosphorylation of p70S6K, an effector of mTORC1, suggests T1R3 ablation reduces mTORC1 activity by approximately 50% in the male livers. Collectively, these findings suggest that the whole-body deletion of T1R3 reduces atherosclerosis and hepatic steatosis in a manner largely independent of the measured effects on whole-body glucose and lipid homeostasis. [ABSTRACT FROM AUTHOR]

Aim: Pinnipeds are thought to have evolved from a North Pacific ancestor, although some fossil evidence suggests a nonmarine Arctic origin and separate invasions into the North Pacific and North Atlantic. We here set out to test differing hypotheses about the origin of pinnipeds through identification and age estimation of pinniped marine invasions. Location: Arctic, North America, North Atlantic, North Pacific. Taxon: Pinnipeds (seals, sea lions, walruses and their fossil relatives). Methods: Because evidence indicates that taste loss in marine mammals and birds results from adaptation to the marine environment, we examined 16 representative pinnipeds for loss‐of‐function mutations in the TAS1R1, TAS1R2 and TAS1R3 genes encoding the sweet T1R2–T1R3 and umami (savory) T1R1–T1R3 receptors, and used the loss‐of‐function events of these receptors as indicators of marine invasion. Results: Numerous loss‐of‐function mutations were found in each pinniped TAS1R (22 in TAS1R1, 21 in TAS1R2 and 42 in TAS1R3). Six mutations were shared by all phocids and six other mutations by all otarioids (otariids and odobenids), but none by all phocids and all otarioids. Selective pressures on TAS1R1, TAS1R2 and TAS1R3 were estimated to have been relaxed, respectively, 16.3, 20.1 and 19.8 million years ago (Myra) in phocids, and 12.1, 18.1 and 18.2 Myra in otarioids. Main conclusions: All TAS1Rs, T1R1–T1R3 and T1R2–T1R3 are nonfunctional in all extant pinnipeds. Both receptors lost their function approximately 20 Myra in the Phocidae lineage and approximately 18 Myra in the Otarioidea lineage. Both lineages have colonized the marine realm independently, which entails nonmarine origins of both Pinnipedia and its stem lineage. Combined with fossil evidence, molecular findings here suggest an Arctic centre of long‐lasting (approximately 38–18 Myra) nonmarine pinniped evolution and at least five separate marine invasions, with the extinct (enaliarctid, Desmatophocidae, Kolponomos) and Otarioidea lineages entering the North Pacific and the Phocidae lineage the North Atlantic. [ABSTRACT FROM AUTHOR]

Context: Sweet taste receptors (STRs) involve in regulating the release of glucose-stimulated glucagon-like peptide-1 (GLP-1). Our in vivo and in vitro studies found that 3-deoxyglucosone (3DG) inhibited glucose-stimulated GLP-1 secretion. Objective: This study investigated the role of STRs in 3DG-induced inhibition of high glucose-stimulated GLP-1 secretion. Methods: STC-1 cells were incubated with lactisole or 3DG for 1 h under 25 mM glucose conditions. Western blotting was used to study the expression of STRs signaling molecules and ELISA was used to analyse GLP-1 and cyclic adenosine monophosphate (cAMP) levels. Results: Lactisole inhibited GLP-1 secretion. Exposure to 25 mM glucose increased the expressions of STRs subunits when compared with 5.6 mM glucose. 3DG decreased GLP-1 secretion and STRs subunits expressions, with affecting other components of STRs pathway, including the downregulation of transient receptor potential cation channel subfamily M member 5 (TRPM5) expression and the reduction of intracellular cAMP levels. Conclusion: 3DG attenuates high glucose-stimulated GLP-1 secretion by reducing STR subunit expression and downstream signaling components. [ABSTRACT FROM AUTHOR]

Childhood obesity is a major public health problem. It has a direct impact on the quality of life of children and adolescents, as well as on their future risk of developing chronic diseases. Dietary patterns rich in fats and sugars and lacking dietary fibers, vitamins, and minerals, as well as lack of physical exercise have been associated with the rise of obesity prevalence. However, factors that contribute to the preference for foods rich in these nutrients are not well established. Taste is recognized as an important predictor of food choices, and polymorphisms in taste-related genes may explain the variability of taste preference and food intake. The aim of this research is to evaluate the influence of polymorphisms of the sweet taste receptor gene TAS1R2 on diet and metabolic profile in obese children and adolescents. A cross-sectional study with 513 obese children and adolescents and 135 normal-weight children was carried out. A molecular study was performed for the single nucleotide polymorphisms (SNPs) rs9701796 and rs35874116 of TAS1R2, and dietary intake, anthropometric parameters (weight, height, waist circumference, waist-to-height ratio (WHtR)), and metabolic profile (including fasting glucose, insulin, triglyceride, high-density lipoprotein (HDL)--cholesterol, and leptin levels) were analyzed. The variant rs9701796 was associated with increased waist-height ratio, as well as with a higher chocolate powder intake in obese children. The variant rs35874116 was associated with a lower dietary fiber intake. In conclusion, there was no relationship between genotypes and risk of obesity. Obese adolescents carrying the serine allele of SNP rs9701796 in TAS1R2 showed higher waist-to-height ratio and chocolate powder intake, whereas those carrying the valine allele of SNP rs35874116 in TAS1R2 were characterized by lower dietary fiber intake. [ABSTRACT FROM AUTHOR]

The taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors participates in monitoring energy and nutrient status. TAS1R member 3 (TAS1R3) is a bi-functional protein that recognizes amino acids such as L-glycine and L-glutamate or sweet molecules such as sucrose and fructose when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively. It was recently reported that deletion of TAS1R3 expression in Tas1R3 mutant mice leads to increased cortical bone mass but the underlying cellular mechanism leading to this phenotype remains unclear. Here, we independently corroborate the increased thickness of cortical bone in femurs of 20-week-old male Tas1R3 mutant mice and confirm that Tas1R3 is expressed in the bone environment. Tas1R3 is expressed in undifferentiated bone marrow stromal cells (BMSCs) in vitro and its expression is maintained during BMP2-induced osteogenic differentiation. However, levels of the bone formation marker procollagen type I N-terminal propeptide (PINP) are unchanged in the serum of 20-week-old Tas1R3 mutant mice as compared to controls. In contrast, levels of the bone resorption marker collagen type I C-telopeptide are reduced greater than 60% in Tas1R3 mutant mice. Consistent with this, Tas1R3 and its putative signaling partner Tas1R2 are expressed in primary osteoclasts and their expression levels positively correlate with differentiation status. Collectively, these findings suggest that high bone mass in Tas1R3 mutant mice is due to uncoupled bone remodeling with reduced osteoclast function and provide rationale for future experiments examining the cell-type-dependent role for TAS1R family members in nutrient sensing in postnatal bone remodeling. [ABSTRACT FROM AUTHOR]

Individual differences in taste perception may influence appetite, dietary intakes, and subsequently, disease risk. Correlations of DNA methylation patterns at taste transducing genes with BMI and dietary intakes were studied. A nutriepigenomic analysis within the Methyl Epigenome Network Association (MENA) project was conducted in 474 adults. DNA methylation in peripheral white blood cells was analyzed by a microarray approach. KEGG pathway analyses were performed concerning the characterization and discrimination of genes involved in the taste transduction pathway. Adjusted FDR values (p < 0.0001) were used to select those CpGs that showed best correlation with BMI. A total of 29 CpGs at taste transducing genes met the FDR criteria. However, only 12 CpGs remained statistically significant after linear regression analyses adjusted for age and sex. These included cg15743657 (TAS1R2), cg02743674 (TRPM5), cg01790523 (SCN9A), cg15947487 (CALHM1), cg11658986 (ADCY6), cg04149773 (ADCY6), cg02841941 (P2RY1), cg02315111 (P2RX2), cg08273233 (HTR1E), cg14523238 (GABBR2), cg12315353 (GABBR1) and cg05579652 (CACNA1C). Interestingly, most of them were implicated in the sweet taste signaling pathway, except CACNA1C (sour taste). In addition, TAS1R2 methylation at cg15743657 was strongly correlated with total energy (p < 0.0001) and carbohydrate intakes (p < 0.0001). This study suggests that methylation in genes related to sweet taste could be an epigenetic mechanism associated with obesity. [ABSTRACT FROM AUTHOR]

Objective: Dental caries is one of the most frequent multifactorial diseases. Among the numerous factors influencing the risk of caries, genetics plays a substantial role, with heritability ranging from 40 to 60%. Gene variants affecting taste preference and glucose transport were recently associated with caries risk. The aim of this study was to analyze two common polymorphisms in the sweet taste receptor (TAS1R2) and glucose transporter (GLUT2) genes in children with dental caries and healthy controls in the Czech population. Methods: A total of 637 unrelated Caucasian children, aged 11-13 years, were included in this case-control study. One hundred and fifty-five subjects were caries-free (with decayed/missing/filled teeth, DMFT = 0) and 482 children were caries-affected (DMFT ≥ 1). The TAS1R2 (Ile191Val, rs35874116) and GLUT2 (Thr110Ile, rs5400) genotypes were determined using the 5′ nuclease TaqMan® assay for allelic discrimination. Results: Compared with subjects with the common Thr allele, carriers of the Ile allele of GLUT2 had significantly more frequently dental caries (p < 0.05, OR = 1.639, 95% CI: 1.089-2.466). Similarly, children with the Val allele for the TAS1R2 Ile191Val polymorphism were more frequently affected by caries than children who carried the Ile allele (p < 0.05, OR = 1.413, 95% CI: 1.014-1.969). In contrast, no significant associations between GLUT2 and/or TAS1R2 polymorphisms and fillings were found, but allele frequencies of the TAS1R2 variant were marginally significantly different between children with DMFT = 0 and DMFT ≥1 (p = 0.053, OR = 1.339, 95% CI: 0.996-1.799). However, no significant interaction between both genes and risk of dental caries was found. Conclusions: In conclusion, GLUT2 and TASR1 polymorphisms may influence the risk of caries in the Czech population. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Highlights: [•] We tested the effect of lipopolysaccharide (LPS) on peripheral taste responses. [•] Ingested LPS selectively and transiently inhibited neural responses to sucrose. [•] Neural effects were TLR4-dependent and accompanied by reduced T1R2+3 expression. [•] Limited exposure to a bacterial component alters taste input to the CNS. [ABSTRACT FROM AUTHOR]

Evidence in the literature supports the hypothesis that the T1R2+3 heterodimer binds to compounds that humans describe as sweet. Here, we assessed the necessity of the T1R2 and T1R3 subunits in the maintenance of normal taste sensitivity to carbohydrate stimuli. We trained and tested water-restricted T1R2 knockout (KO), T1R3 KO and their wild-type (WT) same-sex littermate controls in a two-response operant procedure to sample a fluid and differentially respond on the basis of whether the stimulus was water or a tastant. Correct responses were reinforced with water and incorrect responses were punished with a time-out. Testing was conducted with a modified descending method of limits procedure across daily 25-min sessions. Both KO groups displayed severely impaired performance and markedly decreased sensitivity when required to discriminate water from sucrose, glucose, or maltose. In contrast, when Polycose was tested, KO mice had normal EC50 values for their psychometric functions, with some slight, but significant, impairment in performance. Sensitivity to NaCl did not differ between these mice and their WT controls. Our findings support the view that the T1R2+3 heterodimer is the principal receptor that mediates taste detection of natural sweeteners, but not of all carbohydrate stimuli. The combined presence of T1R2 and T1R3 appears unnecessary for the maintenance of relatively normal sensitivity to Polycose, at least in this task. Some detectability of sugars at high concentrations might be mediated by the putative polysaccharide taste receptor, the remaining T1R subunit forming either a homodimer or heteromer with another protein(s), or nontaste orosensory cues. [ABSTRACT FROM AUTHOR]

Taste perception is an important component of an animal's fitness. The identification of vertebrate taste receptor genes in the last decade has enabled molecular genetic studies of the evolution of taste perception in the context of the ecology and dietary preferences of organisms. Although such analyses have been conducted in a number of species for bitter taste receptors, a similar analysis of sweet taste receptors is lacking. Here, we survey the sole sweet taste–specific receptor gene Tas1r2 in 42 bat species that represent all major lineages of the order Chiroptera, one of the most diverse groups of mammals in terms of diet. We found that Tas1r2 is under strong purifying selection in the majority of the bats studied, with no significant difference in the strength of the selection between insect eaters and fruit eaters. However, Tas1r2 is a pseudogene in all three vampire bat species and the functional relaxation likely started in their common ancestor, probably due to the exclusive feeding of vampire bats on blood and their reliance on infrared sensors rather than taste perception to locate blood sources. Our survey of available genome sequences, together with previous reports, revealed additional losses of Tas1r2 in horse, cat, chicken, zebra finch, and western clawed frog, indicating that sweet perception is not as conserved as previously thought. Nonetheless, we found no common dietary pattern among the Tas1r2-lacking vertebrates, suggesting different causes for the losses of Tas1r2 in different species. The complexity of the ecological factors that impact the evolution of Tas1r2 calls for a better understanding of the physiological roles of sweet perception in different species. [ABSTRACT FROM PUBLISHER]

Sweet taste receptors (STR) are expressed in the gut and other extra-oral tissues, suggesting that STR-mediated nutrient sensing may contribute to human physiology beyond taste. A common variant (Ile191Val) in the TAS1R2 gene of STR is associated with nutritional and metabolic outcomes independent of changes in taste perception. It is unclear whether this polymorphism directly alters STR function and how it may contribute to metabolic regulation. We implemented a combination of in vitro biochemical approaches to decipher the effects of TAS1R2 polymorphism on STR function. Then, as proof-of-concept, we assessed its effects on glucose homeostasis in apparently healthy lean participants. The Ile191Val variant causes a partial loss of function of TAS1R2 through reduced receptor availability in the plasma membrane. Val minor allele carriers have reduced glucose excursions during an OGTT, mirroring effects previously seen in mice with genetic loss of function of TAS1R2. These effects were not due to differences in beta-cell function or insulin sensitivity. Our pilot studies on a common TAS1R2 polymorphism suggest that STR sensory function in peripheral tissues, such as the intestine, may contribute to the regulation of metabolic control in humans. • Sweet taste receptors (STR) have functional roles beyond taste perception. • The TAS1R2 gene of STR is highly polymorphic, suggesting nutrient-dependent adaptive roles. • The Ile191Val variant of TAS1R2 gene causes a partial STR loss-of-function. • Val carriers have reduced glucose excursions mirroring TAS1R2-KO mice. [ABSTRACT FROM AUTHOR]

Abstract: Humans will eat almost anything, from caribou livers to rutabagas, but there are some types of foods, and their associated taste qualities, that are preferred by large groups of people regardless of culture or experience. When many choices are available, humans chose foods that taste good, that is, create pleasing sensations in the mouth. The concept of good taste for most people encompasses both flavor and texture of food, and these sensations merge with taste proper to form the concept of goodness. Although we acknowledge the universality of the goodness (sweet) or badness (bitter) of basic taste qualities, we also find that people differ, sometimes extremely so, in their ability to perceive and enjoy these qualities and, by extension, food and drink. The reasons for these differences among people are not clear but are probably due to a combination of experience beginning at an early age, perhaps in utero; learning, for example, as with conditioned taste aversions; sex and maturity; and perceptual differences that arise from genetic variation. In this review, we focus on individual variations that arise from genetic differences and review two domains of science: recent developments in the molecular biology of taste transduction, with a focus on the genes involved and second, studies that examine biological relatives to determine the heritability of taste perception. Because the receptors for sweet, savory (umami), and bitter have recently been discovered, we summarize what is known about their function by reviewing the effect of naturally occurring and man-made alleles of these receptors, their shape and function based on receptor modeling techniques, and how they differ across animal species that vary in their ability to taste certain qualities. We discuss this literature in the context of how taste genes may differ among people and give rise to individuated taste experience, and what is currently known about the genetic effects on taste perception in humans. [Copyright &y& Elsevier]

The detection of energy-rich sweet food items has been important for our survival during evolution, however, in light of the changing lifestyles in industrialized and developing countries our natural sweet preference is causing considerable problems. Hence, it is even more important to understand how our sense of sweetness works, and perhaps even, how we may deceive it for our own benefit. This chapter summarizes current knowledge about sweet tastants and sweet taste modulators on the compound side as well as insights into the structure and function of the sweet taste receptor and the transduction of sweet signals. Moreover, methods to assess the activity of sweet substances in vivo and in vitro are compared and discussed., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Taste receptor type 1, member 2 (TAS1R2) controls the oral sensing of sweetness. Genetic variations in TAS1R2 have been shown to be associated with differential sweetness intensity and varying carbohydrate intake levels among individuals. This study examined whether rs7534618 A > C in TAS1R2 is associated with dietary behavior and energy nutrient intake in Korean females. A cross-sectional design utilizing data from the Multi-Rural Communities Cohort Study, which was a nationwide epidemiological research project in Korea, was applied in this study. In total, 2198 females were analyzed to evaluate the differences in macronutrient intake levels and intake of carbohydrate-rich and sweet-tasting foods between the rs7534618 genotypes. The findings suggest that individuals with the CC minor genotype tended to have lower carbohydrate but higher fat intake than subjects with the A* genotype (p = 0.035 and p = 0.042, respectively). Subjects with the CC genotype also exhibited less intake of total grains but greater intake of bread than those with the A* genotype (p = 0.017 and p = 0.006, respectively). However, these observed associations were statistically modest (false discovery rate adjusted p > 0.05). In conclusion, TAS1R2 rs7534618 is not a decisive genetic modifier of nutrition and dietary intake in Korean females. However, given the paucity of studies, these putative associations between the TAS1R variation and dietary intake may be referred for further sensory genetic studies in Koreans., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

• Docking to homology models of VFT domain of human T1R2 was evaluated. • Medaka fish-based model performed well for compounds below 460 g/mol. • Model based on open form experimental structures was useful for larger compounds. • Screening of FooDB retrieved recently patented sweeteners and provides novel candidates. Sweet taste is a cue for calorie-rich food and is innately attractive to animals, including humans. In the context of modern diets, attraction to sweetness presents a significant challenge to human health. Most known sugars and sweeteners bind to the Venus Fly Trap domain of T1R2 subunit of the sweet taste heterodimer. Because the sweet taste receptor structure has not been experimentally solved yet, a possible approach to finding sweet molecules is virtual screening using compatibility of candidate molecules to homology models of sugar-binding site. Here, the constructed structural models, docking and scoring schemes were validated by their ability to rank known sweet-tasting compounds higher than properties-matched random molecules. The best performing models were next used in virtual screening, retrieving recently patented sweeteners and providing novel predictions. [ABSTRACT FROM AUTHOR]