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Objectives 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. Methods This study included 205 adults whose detailed intraoral health examination was completed and decayed, missing, filled teeth (DMFT) index values were recorded. A mini questionnaire was applied to assess the consumption of bitter and sweet food. A venous blood sample from each participant was collected in Ethylenediamine tetraacetic acid (EDTA) tubes. Further, DNA samples were isolated from the blood samples by utilizing a DNA isolation kit, which were stored at +4 °C prior to the analysis. Taste receptor type 2 member 38 (TAS2R38; rs10246939, rs713598, rs1726866), Taste receptor type 1 member 2 (TAS1R2; rs35874116, rs9701796), and Taste receptor type 1 member 3 (TAS1R3; rs307355) gene polymorphisms were detected using real-time polymerase chain reaction (PCR). Results There was no statistically significant association between the TAS2R38, TAS1R2, and TAS1R3 gene polymorphism and the DMFT index (p>0.05). No significant difference was found between the consumption of bitter and sweet food and the DMFT index (p>0.05). Conclusions TAS2R38 (rs10246939, rs713598, rs1726866), TAS1R2 (rs35874116, rs9701796), and TAS1R3 (rs307355) gene polymorphism may not be associated with the formation of dental caries in the Turkish adult population.

Increased sugar intake and taste dysfunction have been reported in patients with inflammatory bowel disease (IBD), a chronic disorder characterized by diarrhea, pain, weight loss and fatigue. It was previously unknown whether taste function changes in mouse models of IBD. Mice consumed dextran sodium sulfate (DSS) during three 7-day cycles to induce chronic colitis. DSS-treated mice displayed signs of disease, including significant weight loss, diarrhea, loss of colon architecture, and inflammation of the colon. After the last DSS cycle we assessed taste function by recording electrophysiological responses from the chorda tympani (CT) nerve, which transmits activity from lingual taste buds to the brain. DSS treatment significantly reduced neural taste responses to natural and artificial sweeteners. Responses to carbohydrate, salt, sour or bitter tastants were unaffected in mice with colitis, but umami responses were modestly elevated. DSS treatment modulated the expression of receptor subunits that transduce sweet and umami stimuli in oral taste buds as a substrate for functional changes. Dysregulated systemic cytokine responses, or dysbiosis that occurs during chronic colitis may be upstream from changes in oral taste buds. We demonstrate for the first time that colitis alters taste input to the brain, which could exacerbate malnutrition in IBD patients., Competing Interests: Conflict of interest statement: The authors declare no competing financial interests.

Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analysed GWAS data on confection consumption using 14 073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative FFQ to estimate food intake that was validated previously. Association of the imputed variants with confection consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1–3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/d) in addition to the above-described variables. We found 418 SNP located in 12q24 that were associated with confection consumption. SNP with the ten lowest P-values were located on nine genes including at the BRAP, ACAD10 and aldehyde dehydrogenase 2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with confections intake with genome-wide significance. In conclusion, we found a significant number of SNP located on 12q24 genes that were associated with confections intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake.

Human taste threshold measurements often are used to infer tastant receptor functionality. However, taste thresholds can be influenced by receptor-independent variables. Examination of the full range of taste-active concentrations by taste discrimination has been hampered by logistics of testing multiple concentrations in replicate with human subjects. We developed an automated rapid throughput operant methodology for taste discrimination and applied it to concentration-response analysis of human taste. Tastant solutions (200 µl) drawn from a 96-well plate and self-administered to the tongue served as discriminative stimuli for money-reinforced responses on a touch-sensitive display. Robust concentration-response functions for "basic taste" stimuli were established, with particular focus on agonists of the taste 1 receptor member 2-taste 1 receptor member 3 heterodimer receptor (TAS1R2/R3). With a training cue of 100 mM sucrose, EC50 values of 56, 79, and 310 µM and 40 mM were obtained for rebaudioside A, sucralose, acesulfame potassium, and sucrose, respectively. Changing the sucrose training cue to 300 mM had no impact, but changing to 30 mM resulted in slight leftward shifts in potencies. A signal detection method also was used to determine values of d', a probabilistic value for discriminability, which indicated that 5 mM was near the limits of detection for sucrose. With repeated testing, both EC50 values and 5 mM sucrose d' values were established for each individual subject. The results showed little correspondence between threshold sensitivities and EC50 values for sucrose. We conclude that concentration-response analysis of taste discrimination provides a more reliable means of inferring receptor function than measurement of discriminability at the lowest detectable tastant concentrations. SIGNIFICANCE STATEMENT: Many inferences about human tastant receptor functionality have been made from taste threshold measurements, which can be influenced by variables unrelated to receptors. We herein report a new methodology that enables rigorous concentration-response analysis of human taste discrimination and its use toward quantitative characterization of tastant agonist activity. Our data suggest that taste discrimination concentration-response functions are a more reliable reflection of underlying receptor activity than threshold measures obtained at the lowest detectable tastant concentrations.

Human sweet taste receptor (hSTR) recognizes a wide array of sweeteners, resulting in sweet taste perception. Maltitol and lactitol have been extensively used in place of sucrose due to their capability to prevent dental caries. Herein, several molecular modeling approaches were applied to investigate the structural and energetic properties of these two polyols/hSTR complexes. Triplicate 500 ns molecular dynamics (MD) simulations and molecular mechanics/generalized Born surface area (MM/GBSA)-based free energy calculations revealed that the TAS1R2 monomer is the preferential binding site for maltitol and lactitol rather than the TAS1R3 region. Several polar residues (D142, S144, Y215, D278, E302, R383, and especially N143) were involved in polyols binding through electrostatic attractions and H-bond formations. The molecular complexation process not only induced the stable form of ligands but also stimulated the conformational adaptation of the TAS1R2 monomer to become a close-packed structure through an induced-fit mechanism. Notably, the binding affinity of the maltitol/TAS1R2 complex (ΔGbind of -17.93 ± 1.49 kcal/mol) was significantly higher than that of the lactitol/TAS1R2 system (-8.53 ± 1.78 kcal/mol), in line with the experimental relative sweetness. These findings provide an in-depth understanding of the differences in the sweetness response between maltitol and lactitol, which could be helpful to design novel polyol derivatives with higher sweet taste perception.

We hypothesized that subjects with genetic variants that increase sweet taste preference would consume more sucrose‐containing foods and have altered energy and glucose metabolisms, which would have interactions with lifestyles. Korean genome and epidemiology study (KoGES) was conducted to determine genetic variants and lifestyles including nutrient intakes by the Korean Center for Disease and Control during 2004–2013. Subjects were 8,842 adults aged 40–69 years in Ansan/Ansung cohorts in Korea. The associations between genetic risk scores(GRS) selected for influencing higher sweet preference and energy and glucose metabolism were examined using logistic regression after adjusting for covariates. GRS included 8 SNPs, TAS1R2_rs61761364, SLC2A5_rs11121306, SLC2A7_ rs769902, SLC2A5_rs765618, TRPM5_rs1965606, TRPV1_rs224495, TRPV1_ rs8065080, and TRPV1_rs8078502. Sweet taste preference was higher by 1.30‐folds in high GRS than in low GRS (p, Eight genetic variants associated with sweet taste preference were selected in the genes involved in taste receptor signaling. Adults carrying genetically high sweet taste preferences were associated with consuming higher sucrose‐containing food intakes and improving glucose tolerance. High mental stress and lack of physical activity quenched the genetic impact.

The sweet taste is elicited by activation of the TAS1R2/1R3 heterodimer G protein-coupled receptor. This is a therapeutic target for treatment of obesity and metabolic dysfunctions. Sweetener blends provide attractive strategies to lower the sugar level while preserving the attractive taste of food. To understand the synergic effect of various sweetener blend combinations of artificial and natural sweeteners, we carried out our molecular dynamics studies using predicted structures of the TAS1R2/1R3 heterodimer and predicted structures for the sweeteners. We used as a measure of activation the intracellular ionic lock distance between transmembrane helices 3 and 6 of TAS1R3. We find that full synergic combinations [rebaudioside A (Reb-A)/acesulfame K and Reb-A/sucralose] and partial synergic combinations (sucralose/acesulfame K) show significantly more negative changes in the free energy compared to single-ligand cases, while a pair known to be suppressive (saccharin and acesulfame K) shows significantly less changes than for the single-ligand case. This study provides an atomistic understanding of the mechanism for synergy and identifies new combinations of sweeteners to reduce the caloric content for treating diseases.

The Tas1R3 G protein-coupled receptor constitutes the main component of sweet taste sensory response in humans via forming a heterodimer with Tas1R2 or a homodimer with Tas1R3. The Tas1R3/1R3′ homodimer serves as a low-affinity sweet taste receptor, stimulating gustducin G protein (G_(Gust)) signaling in the presence of a high concentration of natural sugars. This provides an additional means to detect the taste of natural sugars, thereby differentiating the flavors between natural sugars and artificial sweeteners. We report here the predicted 3D structure of active state Tas1R3/1R3′ homodimer complexed with heterotrimeric GGust and sucrose. We discovered that the G_(Gust) makes ionic anchors to intracellular loops 1 and 2 of Tas1R3 while the Gα–α5 helix engages the cytoplasmic region extensively through salt bridge and hydrophobic interactions. We show that in the activation of this complex the Venus flytrap domains of the homodimer undergo a remarkable twist up to ∼100° rotation around the vertical axis to adopt a closed–closed conformation while the intracellular region relaxes to an open–open conformation. We find that binding of sucrose to the homodimer stabilizes a preactivated conformation with a largely open intracellular region that recruits and activates the G_(Gust). Upon activation, the Gα subunit spontaneously opens up the nucleotide-binding site, making nucleotide exchange facile for signaling. This activation of G_(Gust) promotes the interdomain twist of the Venus flytrap domains. These structures and transformations could potentially be a basis for the design of new sweeteners with higher activity and less unpleasant flavors.

It has recently been shown that taste receptors, in addition to being present in the oral cavity, exist in various extra-oral organs and tissues such as the thyroid, lungs, skin, stomach, intestines, and pancreas. Although their physiological function is not yet fully understood, it appears that they can help regulate the body's homeostasis and provide an additional defense function against pathogens. Since the vast majority of drugs are bitter, the greatest pharmacological interest is in the bitter taste receptors. In this review, we describe how bitter taste 2 receptors (TAS2Rs) induce bronchodilation and mucociliary clearance in the airways, muscle relaxation in various tissues, inhibition of thyroid stimulating hormone (TSH) in thyrocytes, and release of glucagon-like peptide-1 (GLP-1) and ghrelin in the digestive system. In fact, substances such as dextromethorphan, chloroquine, methimazole and probably glimepiride, being agonists of TAS2Rs, lead to these effects. TAS2Rs and taste 1 receptors (TAS1R2/3) are G protein-coupled receptors (GPCR). TAS1R2/3 are responsible for sweet taste perception and may induce GLP-1 release and insulin secretion. Umami taste receptors, belonging to the same superfamily of receptors, perform a similar function with regard to insulin. The sour and salty taste receptors work in a similar way, both being channel receptors sensitive to amiloride. Finally, gene-protein coupled receptor 40 (GPR40) and GPR120 for fatty taste perception are also protein-coupled receptors and may induce GLP-1 secretion and insulin release, similar to those of other receptors belonging to the same superfamily.

The human sweet taste receptor is a TAS1R2/TAS1R3 heterodimer. To investigate the correlation between the in vitro affinity of sweeteners with stably expressed human sweet taste receptor in HEK-293 cells and human sensory evaluation, the receptor-ligand activity of bulk (sucrose, D-fructose, and allulose) and high-intensity sweeteners (saccharin, rebaudioside A, rebaudioside M, and neohesperidin dihydrochalcone) was compared by analyzing the Ca(2+) release. The relative potency of the sweeteners was identified over a wide concentration range for EC(50)s. Relative to sucrose, bulk sweeteners showed similar concentration ranges and potency, whereas high-intensity sweeteners exhibited lower concentration ranges and higher potency. The log of the calculated EC(50) of each sweetener relative to sucrose by the in vitro affinity assay was positively correlated (r = 0.9943) with the molar relative sweetness reported in the previous literatures. These results suggested a good correlation between the in vitro activity assay of sweeteners and human sensory evaluation.

Despite brushing and/or flossing their teeth twice daily, many people are still susceptible to dental cavities and tooth decay. This research investigates the genetic and cardiovascular health behind this phenomenon. Two gene variants related to taste pathways, taste 1 receptor member 2 (TAS1R2) and taste 2 receptor member 38 (TAS2R38), were tested on the DNA of 20 students at Northern State University (10 males and 10 females). In concert with genetic screening, tooth impressions were taken of the participants’ upper and lower jaws along with salivary pH, heart rates, and blood pressures. Participants’ cavities and fillings were counted and their gums examined for inflammation. Results showed that seven out of 10 males and two out of 10 females had the gene variant (TAS1R2). Students with this gene variant had an average salivary pH of 5.22—significantly lower than the salivary pH for the other non-carrier students (p < 0.05). These students also had smaller-sized tooth enamel, with none showing a size greater than one millimeter (x̄ = 0.84 millimeters). Students not expressing the gene variant had fewer cavities than those expressing the TAS1R2 gene variant (i.e., one of the regions amplified). Four of the males and both of the females that carried the gene variant also showed signs of swollen gums, possibly contributing to heart disease in the future. Blood pressures and heart rates for the carriers were statistically significant (p < 0.05), showing higher pressures and faster rates compared to non-carriers; meanwhile, all of the non-carriers had normal pressures and rates. Further, body mass index was lower among individuals without the gene variant. The results this limited study indicate that the TAS1R2 gene variant may play a role in cavity development and impact (or indicate poor) cardiovascular health, highlighting the importance of understanding the role of gene variants with regard to risk of tooth decay and gum and heart disease. KEYWORDS: Dental cavities; Tooth decay; Gum and heart disease; Taste pathway gene; Gene variant; Blood pressure; Heart rate; Salivary pH; Tooth enamel

"Bitter" and "sweet" are frequently framed in opposition, both functionally and metaphorically, in regard to affective responses, emotion, and nutrition. This oppositional relationship is complicated by the fact that some molecules are simultaneously bitter and sweet. In some cases, a small chemical modification, or a chirality switch, flips the taste from sweet to bitter. Molecules humans describe as bitter are recognized by a 25-member subfamily of class A G-protein coupled receptors (GPCRs) known as TAS2Rs. Molecules humans describe as sweet are recognized by a TAS1R2/TAS1R3 heterodimer of class C GPCRs. Here we characterize the chemical space of bitter and sweet molecules: the majority of bitter compounds show higher hydrophobicity compared to sweet compounds, while sweet molecules have a wider range of sizes. Importantly, recent evidence indicates that TAS1Rs and TAS2Rs are not limited to the oral cavity; moreover, some bitterants are pharmacologically promiscuous, with the hERG potassium channel, cytochrome P450 enzymes, and carbonic anhydrases as common off-targets. Further focus on polypharmacology may unravel new physiological roles for tastant molecules.

Naturally occurring sugars usually have d -chirality. While a change in chirality typically affects ligand–receptor interaction, non-caloric l -glucose was reported as sweet for humans. Here we show that l- and d -glucose have similar sensory detection thresholds (0.041 ± 0.006 M for d -glucose, and 0.032 ± 0.007 M for l- glucose) and similar sweetness intensities at suprathreshold concentrations. We demonstrate that l- glucose acts via the sweet taste receptor TAS1R2/TAS1R3, eliciting a dose-dependent activation in cell-based functional assays. Computational docking of glucose to the VFT domain of TAS1R2 suggests two sub-pockets, each compatible with each of the enantiomers. While some polar residues (Y103, D142, N143, S144, Y215) are unique for sub-pocket A and others (D307, T326, E382, R383) for sub-pocket B, no interaction is unique for only one enantiomer. The many options for creating hydrogen bonds with the hydroxyl moieties of glucose explain how both enantiomers can fit each one of the sub-pockets.

The first thousand days of life from conception have a significant impact on the health status with short, and long-term effects. Among several anthropometric and maternal lifestyle parameters birth weight plays a crucial role on the growth and neurological development of infants. Recent genome wide association studies (GWAS) have demonstrated a robust foetal and maternal genetic background of birth weight, however only a small proportion of the genetic hereditability has been already identified. Considering the extensive number of phenotypes on which they are involved, we focused on identifying the possible effect of genetic variants belonging to taste receptor genes and birthweight. In the human genome there are two taste receptors family the bitter receptors (TAS2Rs) and the sweet and umami receptors (TAS1Rs). In particular sweet perception is due to a heterodimeric receptor encoded by the TAS1R2 and the TAS1R3 gene, while the umami taste receptor is encoded by the TAS1R1 and the TAS1R3 genes. We observed that carriers of the T allele of the TAS1R1-rs4908932 SNPs showed an increase in birthweight compared to GG homozygotes Coeff: 87.40 (35.13–139.68) p-value = 0.001. The association remained significant after correction for multiple testing. TAS1R1-rs4908932 is a potentially functional SNP and is in linkage disequilibrium with another polymorphism that has been associated with BMI in adults showing the importance of this variant from the early stages of conception through all the adult life.

To understand human taste requires not only physiological studies ranging from receptor mechanisms to brain circuitry, but also psychophysical studies that quantitatively describe the perceptual output of the system. As obvious as this requirement is, differences in research approaches, methodologies, and objectives complicate the ability to meet it. Discussed here is an example of how the discovery two decades ago of a perceptual taste illusion (thermal taste) has led to physiological and psychophysical research on both peripheral and central mechanisms of taste, including most recently a psychophysical study of the heat sensitivity of the human sweet taste receptor TAS1R2/T1R3, and an fMRI study of a possible central gain mechanism that may underlie, in part, differences in human taste sensitivity. In addition to the new data and hypotheses these studies have generated, they illustrate instances of research on taste motivated by evidence derived from different approaches and levels of analysis.

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.

Significance The sense of taste provides key information on diet, but evolution of taste receptor genes in vertebrates is sometimes unable to predict their feeding ecology. Here we use behavioral experiments and functional assays to demonstrate the loss of sweet taste despite the conservation of sweet receptor genes in insectivorous bats. Although sweet taste receptor genes were highly conserved between frugivorous and insectivorous bats at the sequence level, our behavioral experiments revealed dramatic divergence in two bat species with distinct diets: the insectivorous bat showed no preference for natural sugars, whereas the frugivorous bat showed strong preferences for sucrose and fructose. Our cell-based assays from multiple representative bat species across the phylogeny further supported the behavioral preference tests., The evolution of taste perception is usually associated with the ecology and dietary changes of organisms. However, the association between feeding ecology and taste receptor evolution is unclear in some lineages of vertebrate animals. One example is the sweet taste receptor gene Tas1r2. Previous analysis of partial sequences has revealed that Tas1r2 has undergone equally strong purifying selection between insectivorous and frugivorous bats. To test whether the sweet taste function is also important in bats with contrasting diets, we examined the complete coding sequences of both sweet taste receptor genes (Tas1r2 and Tas1r3) in 34 representative bat species. Although these two genes are highly conserved between frugivorous and insectivorous bats at the sequence level, our behavioral experiments revealed that an insectivorous bat (Myotis ricketti) showed no preference for natural sugars, whereas the frugivorous species (Rousettus leschenaultii) showed strong preferences for sucrose and fructose. Furthermore, while both sweet taste receptor genes are expressed in the taste tissue of insectivorous and frugivorous bats, our cell-based assays revealed striking functional divergence: the sweet taste receptors of frugivorous bats are able to respond to natural sugars whereas those of insectivorous bats are not, which is consistent with the behavioral preference tests, suggesting that functional evolution of sweet taste receptors is closely related to diet. This comprehensive study suggests that using sequence conservation alone could be misleading in inferring protein and physiological function and highlights the power of combining behavioral experiments, expression analysis, and functional assays in molecular evolutionary studies.

Taste has strong evolutionary basis in the sense of survival by influencing our behavior to obtain food/medicine or avoid poisoning. It is a complex trait and varies among individuals and distinct populations. We aimed to investigate the association between known genetic factors (673 SNPs) and taste preference in the Lithuanian population, as well as to determine a reasonable method for qualitative evaluation of a specific taste phenotype for further genetic analysis. Study group included individuals representing six ethnolinguistic regions of Lithuania. Case and control groups for each taste were determined according to the answers selected to the taste‐specific and frequency of specific food consumption questions. Sample sizes (case/control) for each taste are as follows: sweetness (55/179), bitterness (82/208), sourness (32/259), saltiness (42/249), and umami (96/190). Genotypes were extracted from the Illumina HumanOmniExpress‐12v1.1 arrays’ genotyping data. Analysis was performed using PLINK v1.9. We found associations between the main known genetic factors and four taste preferences in the Lithuanian population: sweetness—genes TAS1R3, TAS1R2, and GNAT3 (three SNPs); bitterness—genes CA6 and TAS2R38 (six SNPs); sourness—genes PKD2L1, ACCN2, PKD1L3, and ACCN1 (48 SNPs); and saltiness—genes SCNN1B and TRPV1 (five SNPs). We found our questionnaire as a beneficial aid for qualitative evaluation of taste preference. This was the first initiative to analyze genetic factors related to taste preference in the Lithuanian population. Besides, this study reproduces, supports, and complements results of previous limited taste genetic studies or ones that lack comprehensive results concerning distinct (ethnic) human populations., The study explores Lithuanian ethnic group‐specific associations between taste preference and known genetic factors. Study reproduces and complements other studies' results in the taste genetics field. Additionally, a candidate questionnaire as a possible tool for taste preference identification is presented.

Using a two-bottle choice test of short duration, we determined taste preference thresholds for eight substances tasting sweet to humans in three chimpanzees (Pan troglodytes) and four black-handed spider monkeys (Ateles geoffroyi). We found that the chimpanzees significantly preferred concentrations as low as 100-500 mM galactose, 250 mM sorbitol, 0.5-2 mM acesulfame K, 0.5-2.5 mM alitame, 0.5 mM aspartame, 0.2-2 mM sodium saccharin, 0.001-0.2 mM thaumatin, and 0.0025-0.005 mM monellin over tap water. The spider monkeys displayed lower taste preference threshold values, and thus a higher sensitivity than the chimpanzees, with five of the eight substances (2-20 mM galactose, 20-50 mM sorbitol, 0.2-1 mM acesulfame K, 0.002-0.005 mM alitame, and 0.002-0.5 mM sodium saccharin), but were generally unable to perceive the sweetness of the remaining three substances (aspartame, thaumatin, and monellin). The ranking order of sweetening potency of the eight taste substances used here correlates significantly between chimpanzees and humans, but not between spider monkeys and humans. This is in line with genetic findings reporting a higher degree of sequence identity in the Tas1r2 and the Tas1r3 genes coding for the mammalian heterodimer sweet-taste receptor between chimpanzees and humans compared to spider monkeys and humans. Taken together, the findings of the present study support the notion that taste responsiveness for substances tasting sweet to humans may correlate positively with phylogenetic relatedness. At the same time, they are also consistent with the notion that co-evolution between fruit-bearing plants and the sense of taste in animals that serve as their seed dispersers may explain between-species differences in sweet-taste perception.

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.

Taste receptors are not only expressed in the taste buds, but also in other nongustatory tissues, including the reproductive system. Taste receptors can be activated by various tastants, thereby exerting relatively physiologic functions. The aim of this study was to investigate the effects and potential mechanisms underlying ovarian taste receptor activation on progesterone production using saccharin sodium as the receptor agonist in a pseudopregnant rat model. Taste 1 receptor member 2 (TAS1R2) and taste 2 receptor member 31 (TAS2R31) were demonstrated to be abundantly expressed in the corpora lutea of rats, and intraperitoneal injection of saccharin sodium can activate both of them and initiate their downstream signaling cascades. The activation of these ovarian taste receptors promoted nitric oxide (NO) production via endothelial nitric oxide synthase (eNOS). NO production then increased ovarian cyclic guanosine 3′,5′-monophosphate (cGMP) levels, which, in turn, decreased ovarian cyclic adenosine 3′,5′-monophosphate levels. In addition, the activation of ovarian taste receptors induced apoptosis, possibly through NO and mitogen-activated protein kinase signaling. As a result, the activation of ovarian taste receptors reduced the protein expression of steroidogenesis-related factors, causing the inhibition of ovarian progesterone production. In summary, our data suggest that the activation of ovarian taste receptors inhibits progesterone production in pseudopregnant rats, potentially via NO/cGMP and apoptotic signaling.

Chirality plays a key role in biomolecular recognition. Typically, a change in chirality will dramatically affect ligand–receptor binding. However, both d-glucose and its enantiomer l-glucose elicit sweet taste in humans. We show that l- and d-glucose are perceived as similarly sweet by humans, and that in cell-based functional assays, both enantiomers activate the human sweet taste receptor TAS1R2/TAS1R3. We hypothesize that both l- and d-glucose occupy the orthosteric binding site in the VFT domain of TAS1R2. Using induced-fit docking to a homology model of this domain, we identify two subpockets in this binding site. The model suggests that glucose molecules can bind in either of these subpockets, which overlap with the predicted positions of monosaccharide units of sucrose. One subpocket is close to the hinge between the two lobes, and overlaps with aspartame and neotame site, the second subpocket overlaps with that described for sweetness enhancers. These findings suggest a framework for rational design of sweeteners combinations.

Hydrogen to deuterium isotopic substitution has only a minor effect on physical and chemical properties of water and, as such, is not supposed to influence its neutral taste. Here we conclusively demonstrate that humans are, nevertheless, able to distinguish D2O from H2O by taste. Indeed, highly purified heavy water has a distinctly sweeter taste than same-purity normal water and can add to perceived sweetness of sweeteners. In contrast, mice do not prefer D2O over H2O, indicating that they are not likely to perceive heavy water as sweet. HEK 293T cells transfected with the TAS1R2/TAS1R3 heterodimer and chimeric G-proteins are activated by D2O but not by H2O. Lactisole, which is a known sweetness inhibitor acting via the TAS1R3 monomer of the TAS1R2/TAS1R3, suppresses the sweetness of D2O in human sensory tests, as well as the calcium release elicited by D2O in sweet taste receptor-expressing cells. The present multifaceted experimental study, complemented by homology modelling and molecular dynamics simulations, resolves a long-standing controversy about the taste of heavy water, shows that its sweet taste is mediated by the human TAS1R2/TAS1R3 taste receptor, and opens way to future studies of the detailed mechanism of action., Ben Abu, Mason and colleagues use molecular dynamics, cell-based experiments, mouse models, and human subjects to determine that, unlike ordinary water, heavy water tastes sweet to humans, but not mice. Mechanistically, this effect is mediated by the human TAS1R/TAS1R3 sweet taste receptor.

The initial objective of this study was to determine if activation of the sweet taste receptor TAS1R2/TAS1R3 is necessary for perception of sweet thermal taste (swTT). Our approach was to inhibit the receptor with the inverse agonist lactisole using a temperature-controlled flow gustometer. Because all prior studies of thermal taste (TT) used metal thermodes to heat the tongue tip, we first investigated whether it could be generated in heated water. Experiment 1 showed that sweetness could be evoked when deionized water was heated from 20 to 35 °C, and testing with static temperatures between 20 and 35 °C demonstrated the importance of heating from a cool temperature. As in previous studies, thermal sweetness was reported by only a subset of participants, and replicate measurements found variability in reports of sweetness across trials and between sessions. Experiment 2 then showed that exposure to 8 mM lactisole blocked perception of swTT. Confirmation of the involvement of TAS1R2/TAS1R3 led to an investigation of possible sensory and cognitive interactions between thermal and chemical sweetness. Using sucrose as a sweet stimulus and quinine as a nonsweet control, we found that dynamic heating capable of producing thermal sweetness did not increase the sweetness of sucrose compared with static heating at 35 °C. However, swTT was disrupted if trials containing sucrose (but not quinine) were interspersed among heating-only trials. These findings provide new information relevant to understanding the perceptual processes and receptor mechanisms of swTT, as well as the heat sensitivity of sweet taste in general.

This study was performed to evaluate the interplay between dental caries, nutritional status, and genetic polymorphisms in TAS1R1 and TAS1R2 (taste receptor, type 1, member 1 and 2) in preschool children and pre-adolescents. We included 525 subjects (306 preschool children and 219 pre-adolescents). Parents/caregivers answered a self-administered questionnaire about their children’s systemic health, characteristics, oral hygiene habits, and diet. Clinical examination was performed to evaluate dental caries and nutritional status. Saliva samples were collected for DNA extraction. The genotyping of rs17492553 ( TAS1R1 ), rs3935570, and rs4920566 ( TAS1R2 ) polymorphisms was performed using real-time PCR with Taqman Genotyping Master Mix and SNP assay. Both univariate and multivariate Poisson regression analyses with robust variance were used for the data analysis. In preschool children, consumption of sweets between meals increased the prevalence of dental caries by 85% (PR c = 1.85; 95%CI 1.39–2.46; p < 0.001), whereas in pre-adolescents, this prevalence increased by 34% (PR a = 1.34; 95%CI 1.11–1.62; p = 0.002), regardless of genetic polymorphisms . Moreover, individuals carrying at least one allele C in rs17492553 presented 23% more prevalence of dental caries (PR a = 1.23; 95%CI 1.02–1.49 p = 0.030). Nutritional status was not associated with dental caries, neither with genetic polymorphisms . Consumption of sweets between meals increased the prevalence of dental caries. In pre-adolescents, rs17492553 genetic polymorphism in TAS1R1 was associated with dental caries.

For many primates, sweet taste is palatable and is an indicator that the food contains carbohydrates, such as sugars and starches, as energy sources. However, we have found that Asian colobine monkeys (lutungs and langurs) have low sensitivity to various natural sugars. Sweet tastes are recognized when compounds bind to the sweet taste receptor TAS1R2/TAS1R3 in the oral cavity; accordingly, we conducted a functional assay using a heterologous expression system to evaluate the responses of Javan lutung (Trachypithecus auratus) TAS1R2/TAS1R3 to various natural sugars. We found that Javan lutung TAS1R2/TAS1R3 did not respond to natural sugars such as sucrose and maltose. We also conducted a behavioral experiment using the silvery lutung (Trachypithecus cristatus) and Hanuman langur (Semnopithecus entellus) by measuring the consumption of sugar-flavored jellies. Consistent with the functional assay results for TAS1R2/TAS1R3, these Asian colobine monkeys showed no preference for sucrose or maltose jellies. These results demonstrate that sweet taste sensitivity to natural sugars is low in Asian colobine monkeys, and this may be related to the specific feeding habits of colobine monkeys.

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.