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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.

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.

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 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.

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.

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.

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.

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., Highlights • 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.

Objectives Cadherins are a type of adhesion molecule involved in cell–cell recognition and morphogenesis. N-cadherin is predominantly expressed in the nervous system, and is localized at synapses, where it not only plays an adhesive role, but also participates in the regulation of synaptic function and plasticity. Taste cells within taste buds have a limited lifespan, and are replaced on a regular basis. However, little is known regarding the expression pattern of cadherins in taste bud cells. In this study, we examined whether taste bud cells in mouse taste papillae express N-cadherins, and if so, which cell type(s) the N-cadherins are found in. Methods We examined the expression of N-cadherins by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and in situ hybridization. Results RT-PCR results demonstrated that N-cadherins are expressed in the taste bud-containing epithelium of the circumvallate papilla in mice. Based on immunohistochemical analyses, N-cadherins were found to be expressed in a subset of taste bud cells of gustatory papillae. Double-labelling studies showed that N-cadherin co-localizes with α-gustducin, aromatic L-amino acid decarboxylase (AADC), carbonic anhydrase IV (CA4), and phospholipase C β2 (PLCβ2). Conclusions Our study indicated that N-cadherins are expressed in type II and III taste cells. Taken together with results from previous studies, we propose that N-cadherins might play a functional role in the establishment of nerve terminal connections.

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.

Taste perception plays a key role in determining individual food preferences and dietary habits and may influence nutritional status. This study aimed to investigate the association of TAS1R2 (Ile191Val - rs35874116) and TAS1R3 (-1266 C/T - rs35744813) variants with food intake and nutritional status in children followed from birth until 7.7 years old. The nutritional status and food intake data of 312 children were collected at three developmental stages (1, 3.9 and 7.7 years old). DNA was extracted from blood samples and the polymorphisms were analyzed by real-time polymerase chain reactions (qPCR) using hydrolysis probes as the detection method. Food intake and nutritional status were compared among individuals with different single nucleotide polymorphism (SNP) genotypes. At 3.9 years old, children homozygous (Val/Val) for the TAS1R2 Ile191Val polymorphism ingested less sugar and sugar-dense foods than children who were *Ile carriers. This finding demonstrated that a genetic variant of the T1R2 taste receptor is associated with the intake of different amounts of high sugar-content foods in childhood. This association may provide new perspectives for studying dietary patterns and nutritional status in childhood.

Hypothalamic tanycytes are glial-like glucosensitive cells that contact the cerebrospinal fluid of the third ventricle, and send processes into the hypothalamic nuclei that control food intake and body weight. The mechanism of tanycyte glucosensing remains undetermined. While tanycytes express the components associated with the glucosensing of the pancreatic β cell, they respond to nonmetabolisable glucose analogues via an ATP receptor-dependent mechanism. Here, we show that tanycytes in rodents respond to non-nutritive sweeteners known to be ligands of the sweet taste (Tas1r2/Tas1r3) receptor. The initial sweet tastant-evoked response, which requires the presence of extracellular Ca2+, leads to release of ATP and a larger propagating Ca2+ response mediated by P2Y1 receptors. In Tas1r2 null mice the proportion of glucose nonresponsive tanycytes was greatly increased in these mice, but a subset of tanycytes retained an undiminished sensitivity to glucose. Our data demonstrate that the sweet taste receptor mediates glucosensing in about 60% of glucosensitive tanycytes while the remaining 40% of glucosensitive tanycytes use some other, as yet unknown mechanism.

Taste and diet preferences are complex and influenced by both environmental and host traits while affecting both food selection and associated health outcomes. The present study genotyped 94 single nucleotide polymorphisms (SNPs) in previously reported taste and food intake related genes and assessed associations with taste threshold (TT) and preferred intensity (PT) of sweet, sour and bitter, food preferences, habitual diet intake, and caries status in healthy young Swedish men and women (n = 127). Polymorphisms in the GNAT3, SLC2A4, TAS1R1 and TAS1R2 genes were associated with variation in TT and PT for sweet taste as well as sweet food intake. Increasing PT for sweet was associated with increasing preference and intake of sugary foods. Similarly, increasing TT for sour was associated with increasing intake of sour foods, whereas the associations between food preference/intake and TT/PT for bitter was weak in this study group. Finally, allelic variation in the GNAT3, SLC2A2, SLC2A4, TAS1R1 and TAS1R2 genes was associated with caries status, whereas TT, PT and food preferences were not. It was concluded that variations in taste receptor, glucose transporter and gustducin encoding genes are related to taste perception, food preference and intake as well as the sugar-dependent caries disease.

BACKGROUND: Individual differences in human perception of sweetness are partly due to genetics; however, which genes are associated with the perception and the consumption of sweet substances remains unclear. OBJECTIVE: The aim of this study was to verify previous reported associations within genes involved in the peripheral receptor systems (i.e., TAS1R2, TAS1R3, and GNAT3) and reveal novel loci. METHODS: We performed genome-wide association scans (GWASs) of the perceived intensity of 2 sugars (glucose and fructose) and 2 high-potency sweeteners (neohesperidin dihydrochalcone and aspartame) in an Australian adolescent twin sample (n = 1757), and the perceived intensity and sweetness and the liking of sucrose in a US adult twin sample (n = 686). We further performed GWASs of the intake of total sugars (i.e., total grams of all dietary mono- and disaccharides per day) and sweets (i.e., handfuls of candies per day) in the UK Biobank sample (n = ≤174,424 white-British individuals). All participants from the 3 independent samples were of European ancestry. RESULTS: We found a strong association between the intake of total sugars and the single nucleotide polymorphism rs11642841 within the FTO gene on chromosome 16 (P = 3.8 × 10(−8)) and many suggestive associations (P

Background/Aims: To determine whether variation in the TAS1R2 gene affects sucrose taste perception and sugar intake. Methods: Participants were men (n = 238) and women (n = 458) aged 20-29 years. A subset (n = 95) with body mass index (BMI) data available completed a sensory analysis study. A food frequency questionnaire assessed dietary intake, and eight polymorphisms were genotyped (rs12033832, rs12137730, rs35874116, rs3935570, rs4920564, rs4920566, rs7513755 and rs9701796). Sucrose taste thresholds were determined by staircase procedure (solutions: 9 × 10-6 to 0.5 mol/l). Suprathreshold sensitivity to 0.01-1.0 mol/l sucrose solutions was assessed using general Labeled Magnitude Scales. Results: A significant genotype-BMI interaction was observed for rs12033832 (G>A) for suprathreshold sensitivity (p = 0.01) and sugar intake (p = 0.003). Among participants with a BMI ≥25, G allele carriers had lower sensitivity ratings (mean incremental area under the taste sensitivity curve ± SE; GG/GA 54.4 ± 4.1 vs. AA 178.5 ± 66.6; p = 0.006), higher thresholds (GG/GA 9.3 ± 1.1 vs. AA 4.4 ± 4.3 mmol/l; p = 0.004) and consumed more sugars (GG/GA 130 ± 4 vs. AA 94 ± 13 g/day; p = 0.009). G allele carriers with a BMI Conclusion: The rs12033832 single nucleotide polymorphism in TAS1R2 is associated with sucrose taste and sugar intake, but the effect differs depending on BMI.

Animal food intake is primarily controlled by appetite, which is affected by food quality, environment, and the management and status of animal health. Sensing of taste is mediated by taste receptor cells and is central to appetite. Taste receptor cells possess distinctive physiological characteristics that permit the recognition of various stimuli in foods. Thus, cultures of porcine circumvallate papillae cells provide a model for identification of the molecular and functional characteristics of taste receptor cells. In this study, we described the isolation and culture of porcine circumvallate papillae, using tissue explants and enzymatic digestion, and showed continuous viability and expression of pivotal taste marker proteins for more than 9 passages. In addition, cultured cells showed dramatic rises in intracellular calcium upon stimulation with several taste stimuli (sweet, umami, bitter, and fat). These cultures of porcine taste receptor cells provide a useful model for assessing taste preferences of pigs and may elucidate interactions between various taste stimuli.

The extent to which taste receptor specificity correlates with, or even predicts, diet choice is not known. We recently reported that the insensitivity to sweeteners shown by species of Felidae can be explained by their lacking of a functional Tas1r2 gene. To broaden our understanding of the relationship between the structure of the sweet receptors and preference for sugars and artificial sweeteners, we measured responses to 12 sweeteners in 6 species of Carnivora and sequenced the coding regions of Tas1r2 in these same or closely related species. The lion showed no preference for any of the 12 sweet compounds tested, and it possesses the pseudogenized Tas1r2. All other species preferred some of the natural sugars, and their Tas1r2 sequences, having complete open reading frames, predict functional sweet receptors. In addition to preferring natural sugars, the lesser panda also preferred 3 (neotame, sucralose, and aspartame) of the 6 artificial sweeteners. Heretofore, it had been reported that among vertebrates, only Old World simians could taste aspartame. The observation that the lesser panda highly preferred aspartame could be an example of evolutionary convergence in the identification of sweet stimuli.

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.

Stress increases the secretion of glucocorticoids (GCs), potent steroid hormones that exert their effects on numerous target tissues by acting through glucocorticoid receptors (GRs). GC signaling significantly affects ingestive behavior and taste preferences in humans and rodent models, but far less is known about the hormonal modulation of the peripheral sensory system that detects and assesses nutrient content of foods. A previous study linked restraint stress in rats to diminished expression of mRNA for one subunit of the sweet taste receptor (Tas1r3) in taste tissue and reduced gustatory nerve excitation by sweet compounds. Using RT-PCR, we detected mRNAs for GRα in circumvallate taste papillae and in oral epithelium devoid of taste buds (“non-taste” tissue). Further, circumvallate tissue was significantly enriched in GR mRNA compared to non-taste tissue based on quantitative PCR. Histologically, GR protein was expressed in all taste bud populations examined (circumvallate, foliate and fungiform papillae). Using transgenic mice expressing green fluorescent protein, almost all (97%) Tas1r3-positive taste cells (sweet-/umami-sensitive) expressed GR compared to a significantly smaller percentage (89%) of TrpM5-positive taste cells (sweet-, umami- and bitter-sensitive). When mice (n = 4) were restrain stressed, GR protein mobilized to the nucleus in Tas1r3-GFP taste cells (1.7-fold over controls). Our results suggest that GR can be activated in taste receptor cells and may play a role in specific taste qualities (e.g., sweet, umami, and bitter) to shape how the taste system responds to stress.

In taste cells, taste receptors, their coupled G proteins and downstream signalling elements mediate the detection and transduction of sweet, bitter and umami compounds. In some intestinal endocrine cells, taste receptors and gustducin contribute to the release of glucagon-like peptide 1 (GLP-1) and other gut hormones in response to glucose and non-energetic sweeteners. Conversely, taste cells have been found to express multiple hormones typically found in intestinal endocrine cells, e.g. GLP-1, glucagon, somatostatin and ghrelin. In the present study, by immunohistochemistry, multiple subsets of taste cells were found to express GLP-1. The release of GLP-1 from ‘endocrine taste cells’ into the bloodstream was examined. In wild-type mice, even after oesophagectomy and vagotomy, oral stimulation with glucose induced an elevation of GLP-1 levels in the bloodstream within 10 min. Stimulation of taste cell explants from wild-type mice with glucose led to the release of GLP-1 into the medium. Knocking out of the Tas1r3 gene did not eliminate glucose-stimulated GLP-1 release from taste cells in vivo. The present results indicate that a portion of the cephalic-phase rise in circulating GLP-1 levels is mediated by the direct release of GLP-1 from taste cells into the bloodstream.

A fundamental role of the taste system is to discriminate between nutritive and toxic foods. However, it is unknown whether bacterial pathogens that might contaminate food and water modulate the transmission of taste input to the brain. We hypothesized that exogenous, bacterially-derived lipopolysaccharide (LPS), modulates neural responses to taste stimuli. Neurophysiological responses from the chorda tympani nerve, which innervates taste cells on the anterior tongue, were unchanged by acute exposure to LPS. Instead, neural responses to sucrose were selectively inhibited in mice that drank LPS during a single overnight period. Decreased sucrose sensitivity appeared 7 days after LPS ingestion, in parallel with decreased lingual expression of Tas1r2 and Tas1r3 transcripts, which are translated to T1R2+T1R3 subunits forming the sweet taste receptor. Tas1r2 and Tas1r3 mRNA expression levels and neural responses to sucrose were restored by 14 days after LPS consumption. Ingestion of LPS, rather than contact with taste receptor cells, appears to be necessary to suppress sucrose responses. Furthermore, mice lacking the Toll-like receptor (TLR) 4 for LPS were resistant to neurophysiological changes following LPS consumption. These findings demonstrate that ingestion of LPS during a single period specifically and transiently inhibits neural responses to sucrose. We suggest that LPS drinking initiates TLR4-dependent hormonal signals that downregulate sweet taste receptor genes in taste buds. Delayed inhibition of sweet taste signaling may influence food selection and the complex interplay between gastrointestinal bacteria and obesity.

We previously demonstrated that equilibrative nucleoside transporter 1 was expressed in taste cells, suggesting the existence of an adenosine signaling system, but whether or not the expression of an adenosine receptor occurs in rat taste buds remains unknown. Therefore, we examined the expression profiles of adenosine receptors and evaluated their functionality in rat circumvallate papillae. Among adenosine receptors, the mRNA for an adenosine A2b receptor (A2bR) was expressed by the rat circumvallate papillae, and its expression level was significantly greater in the circumvallate papillae than in the non-taste lingual epithelium. A2bR-immunoreactivity was detected primarily in type II taste cells, and partial, but significant expression was also observed in type III ones, but there was no immunoreactivity in type I ones. The cAMP generation in isolated epithelium containing taste buds treated with 500 μM adenosine or 10 μM BAY60-6583 was significantly increased compared to in the controls. These findings suggest that adenosine plays a role in signaling transmission via A2bR between taste cells in rats.

Taste buds are unusual in requiring ATP as a transmitter to activate sensory nerve fibers. In response to taste stimuli, taste cells release ATP, activating purinergic receptors containing the P2X2 and P2X3 subunits on taste nerves. In turn, the released ATP is hydrolyzed to ADP by a plasma membrane nucleoside triphosphate previously identified as nucleoside triphosphate diphosphohydrolase-2 (NTPDase2). In this paper we investigate the role of this ectonucleotidase in the function of taste buds by examining gene-targeted Entpd2-null mice globally lacking NTPDase2. RT-PCR confirmed the absence of NTPDase2, and ATPase enzyme histochemistry reveals no reaction product in taste buds of knockout mice, suggesting that NTPDase2 is the dominant form in taste buds. RT-PCR and immunocytochemistry demonstrated that in knockout mice all cell types are present in taste buds, even those cells normally expressing NTPDase2. In addition, the overall number and size of taste buds are normal in Entpd2-null mice. Luciferin/luciferase assays of circumvallate tissue of knockout mice detected elevated levels of extracellular ATP. Electrophysiological recordings from two taste nerves, the chorda tympani and glossopharyngeal, revealed depressed responses to all taste stimuli in Entpd2-null mice. Responses were more depressed in the glossopharyngeal nerve than in the chorda tympani nerve and involved all taste qualities; responses in the chorda tympani were more depressed to sweet and umami stimuli than to other qualities. We suggest that the excessive levels of extracellular ATP in the Entpd2-knockout animals desensitize the P2X receptors associated with nerve fibers, thereby depressing taste responses.

Adaptive evolution plays a role in the functional divergence and specialization of taste receptors and the sense of taste is thought to be closely related to feeding ecology. To examine whether feeding ecology has shaped the evolution of taste receptor genes in vertebrates, we here focus on Tas1r gene family that encodes umami (Tas1r1 and Tas1r3 heterodimer) and sweet (Tas1r2 and Tas1r3 heterodimer) taste receptors. By searching currently available genome sequences in 48 vertebrates that contain 38 mammals, 1 reptile, 3 birds, 1 frog, and 5 fishes, we found all three members of Tas1rs are intact in most species, suggesting umami and sweet tastes are maintained in most vertebrates. Interestingly, the absence and pseudogenization of Tas1rs were also discovered in a number of species with diverse feeding preferences and distinct phylogenetic positions, indicating widespread losses of umami and/or sweet tastes in these animals, irrespective of their diet. Together with previous findings showing losses of tastes in other vertebrates, we failed to identify common dietary factors that could result in the taste losses. Our results report here suggest the evolution of Tas1rs is more complex than we previously appreciated and highlight the caveat of analyzing sequences predicted from draft genome sequences. Future work for a better understanding of taste receptor function would help uncover what ecological factors have driven the evolution history of Tas1rs in vertebrates.

In gustatory function, communication between four types taste buds cells plays crucial roles. ATP is one of the intercellular signaling molecules in taste buds, and the extracellular ATP fate is regulated by its cellular clearance, but there is little information on it. Therefore, we examined the expression profiles of nucleoside transporters (NTs) as a clearance system for ATP metabolite adenosine in rat circumvallate papillae (CP) by RT-PCR, real-time PCR and immunohistochemistry. Among NTs, mRNA for Ent1 was expressed by the CP, and significantly was greater in the CP as compared with non-CP. ENT1 immunoreactivity was detected in PLC-β2-positive type II (71.0±8.5%), chromogranin-A-positive type III (64.9±7.4%), and SNAP25-positive type III (77.0±10.4%) taste cells, but not in NTPDase2-positive type I ones. These results indicate that ENT1-expressing type II and III taste cells might comprise an adenosine clearance system in taste buds of the CP. ENT1 expression in taste cells is important for elucidation of complicated taste signaling.

Glucagon-like peptide-1 (GLP-1) signaling modulates sweet-taste sensitivity in the mouse. Because circumvallate papillae (CVPs) express both GLP-1 and its receptor, a local regulation has been suggested. However, whether dietary lipids are involved in this regulation, as shown in the gut, is unknown. By using a combination of biochemical, immunohistochemical, and behavioral approaches, the present data i) confirm the role of GLP-1 signaling in the attraction for sucrose, ii) demonstrate that minute quantities of long-chain FAs (LCFAs) reinforce the attraction for sucrose in a GLP-1 receptor-dependent manner, iii) suggest an involvement of the LCFA receptor GPR120 expressed in taste buds in this system, and iv) support the existence of a regulation by GLP-1 of the lipid sensing mediated by lingual CD36. Therefore, oro-sensory detection of LCFAs may affect sweet and fatty taste responsiveness by controlling the secretion of lingual GLP-1. This regulatory loop, probably triggered by the LCFA-GPR120 interaction, might contribute to the high palatability of foods rich both in fat and sugar.

Some high-carbohydrate diets may lead to obesity and multiple metabolic disorders, including hypertriglyceridemia (HTG). This lipid abnormality is considered an important risk factor for cardiovascular disease and type 2 diabetes. The sweet taste receptor TAS1R2 polymorphism (Ile191Val) has been reported to be associated with carbohydrate intake. The aim of this study was to analyze the association of the TAS1R2 gene polymorphism with carbohydrate intake and HTG among the population of West Mexico. In a cross-sectional study, 441 unrelated subjects were analyzed for TAS1R2 genotypes (Ile/Ile, Ile/Val and Val/Val) by an allelic discrimination assay. Biochemical tests and a three-day food record were assessed. The Val/Val genotype carriers had a higher intake of total carbohydrates, fiber and servings of cereals and vegetables than the other genotype carriers. The Val/Val genotype conferred a higher risk for HTG than the Ile/Val and Ile/Ile genotypes (OR = 3.26, 95%CI 1.35–7.86, p = 0.006 and OR = 2.61, 95%CI 1.12–6.07, p = 0.02, respectively). Furthermore, the Val/Val genotype was associated with approximately 30% higher triglycerides compared with Ile/Val and Ile/Ile genotypes (β = 44.09, 95%CI 9.94–78.25, p = 0.01 and β = 45.7, 95%CI 10.85–80.54, p = 0.01, respectively). In conclusion, the Val/Val genotype of TAS1R2 was associated with a higher carbohydrate intake and HTG.

Variability in human taste perception is associated with both genetic and environmental factors. The influence of taste receptor expression on this variability is unknown, in part, due to the difficulty in obtaining human oral tissue that enables quantitative expression measures of taste genes. In a comparison of six current techniques (Oragene RNeasy Kit, Isohelix swab, Livibrush cytobrush, tongue saliva, cheek saliva collection, and fungiform papillae biopsy), we identify the fungiform papillae biopsy is the optimal sampling technique to analyse human taste gene expression. The fungiform papillae biopsy resulted in the highest RNA integrity, enabling amplification of all the assessed taste receptor genes (TAS1R1, TAS1R2, TAS1R3, SCNN1A and CD36) and taste tissue marker genes (NCAM1, GNAT3 and PLCβ2). Furthermore, quantitative expression was observed in a subset of taste genes assessed from the saliva collection techniques (cheek saliva, tongue saliva and Oragene RNA kit). These saliva collection techniques may be useful as a non-invasive alternative sampling technique to the fungiform papillae biopsy. Identification of the fungiform papillae biopsy as the optimal collection method will facilitate further research into understanding the effect of gene expression on variability in human taste perception.

ATP and its metabolites are important for taste signaling in taste buds, and thus a clearance system for them would play critical roles in maintenance of gustatory function. A previous report revealed that mRNAs for ecto-5'-nucleotidase (NT5E) and prostatic acid phosphatase (PAP) were expressed by taste cells of taste buds, and NT5E-immunoreactivity was detected in taste cells. However, there was no information on PAP-immunoreactivity in taste buds. In this study, we examined the expression profile of PAP in rat taste buds. In the isolated rat taste buds, we detected expression of mRNA for PAP, but NT5E was not detected differing from the case of mouse ones (Dando et al., 2012, J Neuroscience). On immunohistochemical analysis, PAP-immunoreactivity was found predominantly in NTPDase2-positive type I and SNAP25-positive type III taste cells, while there were no apparent signals of it in PLC-β2-positive type II, α-gustducin-positive type II, AADC-positive type III and 5HT-positive type III ones. As for NT5E, we could not detect its immunoreactivity in rat taste buds, and co-localization of it with any taste cell markers, although mouse taste buds expressed NT5E as reported previously. These findings suggest that PAP expressed by type I and one of type III taste cells of rats may contribute to metabolic regulation of the extracellular levels of adenine nucleotides in the taste buds of circumvallate papillae, and the regulating mechanisms for adenine nucleotides in taste buds might be different between rats and mice.

Mammalian sweet taste is primarily mediated by the type 1 taste receptor Tas1r2/Tas1r3, whereas Tas1r1/Tas1r3 act as the principal umami taste receptor. Bitter taste is mediated by a different group of G protein-coupled receptors, the Tas2rs, numbering 3 to ∼66, depending on the species. We showed previously that the behavioral indifference of cats toward sweet-tasting compounds can be explained by the pseudogenization of the Tas1r2 gene, which encodes the Tas1r2 receptor. To examine the generality of this finding, we sequenced the entire coding region of Tas1r2 from 12 species in the order Carnivora. Seven of these nonfeline species, all of which are exclusive meat eaters, also have independently pseudogenized Tas1r2 caused by ORF-disrupting mutations. Fittingly, the purifying selection pressure is markedly relaxed in these species with a pseudogenized Tas1r2 . In behavioral tests, the Asian otter (defective Tas1r2 ) showed no preference for sweet compounds, but the spectacled bear (intact Tas1r2 ) did. In addition to the inactivation of Tas1r2 , we found that sea lion Tas1r1 and Tas1r3 are also pseudogenized, consistent with their unique feeding behavior, which entails swallowing food whole without chewing. The extensive loss of Tas1r receptor function is not restricted to the sea lion: the bottlenose dolphin, which evolved independently from the sea lion but displays similar feeding behavior, also has all three Tas1r s inactivated, and may also lack functional bitter receptors. These data provide strong support for the view that loss of taste receptor function in mammals is widespread and directly related to feeding specializations.

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-minute intake tests. The functional implications of these results and those in the literature are considered.

Umami taste is responsible for sensing monosodium glutamate, nucleotide enhancers, and other amino acids that are appetitive to vertebrates and is one of the five basic tastes that also include sour, salty, sweet, and bitter. To study how ecological factors, especially diets, impact the evolution of the umami taste, we examined the umami taste receptor gene Tas1r1 in a phylogenetically diverse group of bats including fruit eaters, insect eaters, and blood feeders. We found that Tas1r1 is absent, unamplifiable, or pseudogenized in each of the 31 species examined, including the genome sequences of two species, suggesting the loss of the umami taste in most, if not all, bats regardless of their food preferences. Most strikingly, vampire bats have also lost the sweet taste receptor gene Tas1r2 and the gene required for both umami and sweet tastes (Tas1r3), being the first known mammalian group to lack two of the five tastes. The puzzling absence of the umami taste in bats calls for a better understanding of the roles that this taste plays in the daily life of vertebrates.

To test the possibility that a fast-onset promoting agent repaglinide may initiate prandial insulin secretion through the mechanism of cephalic-phase insulin release, we explored the expression and distribution character of sulfonylurea receptors in rat taste buds. Twenty male Wistar rats aged 10 weeks old were killed after general anesthesia. The circumvallate papillae, fungiform papillae and pancreas tissues were separately collected. Immunohistochemical staining was used to detect the expression and distribution of sulfonylurea receptor 1 (SUR1) or sulfonylurea receptor 2 (SUR2) in rat taste buds. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to analyze the expression of SUR1 or SUR2 mRNA. The pancreatic tissues from the same rat were used as positive control. This is the first study to report that SUR1 is uniquely expressed in the taste buds of fungiform papillae of each rat tongue, while the expression of SUR1 or SUR2 was not detected in the taste buds of circumvallate papillae. SUR1 is selectively expressed in rat taste buds, and its distribution pattern may be functionally relevant, suggesting that the rapid insulin secretion-promoting effect of repaglinide may be exerted through the cephalic-phase secretion pathway mediated by taste buds.

The present study demonstrates the first-ever characterization of cell types that express the vanilloid receptor 1 (VR1) in the taste buds of rat circumvallate papillae. We performed electron microscopy to identify the subcellular location. The VR1 immunoreactivity was associated with the endoplasmic reticulum, cytoplasmic vesicles, and plasma membrane of taste cells. These results demonstrate the localization of the VR1 in membranous structures of the taste cells. We used double immunofluorescence histochemistry with taste cell type-specific markers to identify the cell types that express the VR1. The VR1 was detected in all functional taste cell types (Type I, Type II, and Type III cells). Together, our data suggest that the VR1 might play different roles according to the cell types within a taste bud.

Taste cells are chemosensory epithelial cells that sense distinct taste quality such as umami, sweet, bitter, sour and salty. Taste cells utilize G protein-coupled receptors to detect umami, sweet and bitter taste whereas ion channels are responsible for detecting salty and sour taste. Among these taste receptors, taste receptor type 2, T1R2 (or Tas1r2), has been identified as a sole sweet taste receptor in mammals that mediates sweet signals upon dimerization with T1R3. However, because of limited availability of reliable antibodies and low expression level of G protein-coupled receptors, it is uneasy to identify the cell-types that express these receptors in non-taste tissues. In this study, we have generated a T1R2-LacZ reporter knock-in mouse to investigate tissue distribution of T1R2 at a single-cell level. We found that the LacZ gene expression in these mice was faithful to the expression of T1R2 in the taste tissue and in the gastrointestinal tract where T1R3 expression has been reported. Surprisingly, T1R2 expression was also found in the testis. Mice homozygous for T1R2 deletion lacked T1R2 protein analyzed by the antibody raised against T1R2 peptide sequences. In summary, the T1R2 knock-in mouse is a powerful tool to analyze the putative targets for sweeteners as well as to study the physiological roles of T1R2 in detecting sugars.

Dental caries is influenced by a complex interplay of genetic and environmental factors, including dietary habits. Previous reports have characterized the influence of genetic variation on taste preferences and dietary habits. We therefore hypothesized that genetic variation in taste pathway genes (TAS2R38, TAS1R2, GNAT3) may be associated with dental caries risk and/or protection. Families were recruited by the Center for Oral Health Research in Appalachia (COHRA) for collection of biological samples, demographic data, and clinical assessment of oral health, including caries scores. Multiple single-nucleotide polymorphism (SNP) assays for each gene were performed and analyzed by transmission disequilibrium test (TDT) analysis (FBAT software) for three dentition groups: primary, mixed, and permanent. Statistically significant associations were seen in TAS2R38 and TAS1R2 for caries risk and/or protection.

Sensory systems play an important role in animal survival. Changes to these systems may be critical in evolution of species in new environments. Previous studies exploring the correlation between feeding ecology and Tas1r evolution mainly focused on mammals and birds, and found that the relationship was complex. However, in reptiles, the correlation between Tas1r evolution and dietary preferences is still unclear. Here, we attempted to explore this relationship in representative species of the major groups of reptiles (turtles, snakes, lizards, crocodilians), for which the genome information is known. We first predicted the functionality (intact, partial, or defective) of Tas1r, and then related it to the feeding preferences. As a result, we identified 11 Tas1r1, 12 Tas1r2, and 12 Tas1r3 genes to be partial or intact and another 22 Tas1r genes to be absent or pseudogenized in the 19 reptiles. We found that, as it was revealed in some other vertebrate groups, no correlation existed between feeding ecology and Tas1r evolution in reptiles: genomic prediction indicated that the Tas1r genes possibly have been lost or pseudogenized in snakes, but in crocodylia and testudines Tas1r genes are either intact or partial, regardless of their feeding habits. Thus, we suggest that the driving force of Tas1r evolution in reptiles is complex, and the feeding habit of swallowing food whole without chewing or the absence of taste buds in certain species may account for the possible umami/sweet perception loss. In addition, we propose that caution should be taken when predicting gene functionality from the publicly available genome database.

Sweetness plays an important role in providing calories and promoting appetite for food. Since it has been known that genetic factor(s) is involved in individual differences in taste sensitivity in humans, this study aimed to examine genetic variations of the TAS1R2 gene, one of the components for tasting sweet compounds, by using DNA sequencing analysis from 98 unrelated Korean subjects. As a result, 12 different single nucleotide polymorphisms (SNPs) were identified in the hTAS1R2 gene and most of them were nonsynonymous. Also, two novel SNPs were found for the first time in this study. It was noted that the frequencies of these SNPs were common in the Korean population. 20 different haplotypes with coding SNPs (cSNPs) were also found in this study. Three out of these haplotypes were common, showing frequencies of > 10%. The repertoire and frequencies of cSNPs and haplotypes in the hTAS1R2 gene will provide information that will help identify a functional ligand receptor common in the Korean population.

Snacking is an integral component of eating habits in young children that is often overlooked in nutrition research. While snacking is a substantial source of calories in preschoolers’ diets, there is limited knowledge about the factors that drive snacking patterns. The genetics of taste may help to better understand the snacking patterns of children. The rs1761667 single nucleotide polymorphism (SNP) in the CD36 gene has been linked to fat taste sensitivity, the rs35874116 SNP in the TAS1R2 gene has been related to sweet taste preference, and the rs713598 SNP in the TAS2R38 gene has been associated with aversion to bitter, green leafy vegetables. This study seeks to determine the cross-sectional associations between three taste receptor SNPs and snacking patterns among preschoolers in the Guelph Family Health Study. Preschoolers’ snack quality, quantity, and frequency were assessed using three-day food records and saliva was collected for SNP genotyping (n = 47). Children with the TT genotype in TAS1R2 consumed snacks with significantly more calories from sugar, and these snacks were consumed mostly in the evening. Total energy density of snacks was highest in the CC and CG genotypes compared to the GG genotype in TAS2R38, and also greater in the AA genotype in CD36 compared to G allele carriers, however this difference was not individually attributable to energy from fat, carbohydrates, sugar, or protein. Genetic variation in taste receptors may influence snacking patterns of preschoolers.

The T1R2 and T1R3 proteins are expressed in taste receptor cells and form a heterodimer binding with compounds described as sweet by humans. We examined whether Polycose taste might be mediated through this heterodimer by testing T1R2 knockout (KO) and T1R3 KO mice and their wild-type (WT) littermate controls in a series of brief-access taste tests (25-min sessions with 5-s trials). Sucrose, Na-saccharin, and Polycose were each tested for three consecutive sessions with order of presentation varied among subgroups in a Latin-Square manner. Both KO groups displayed blunted licking responses and initiated significantly fewer trials of sucrose and Na-saccharin across a range of concentrations. KO mice tested after Polycose exposure demonstrated some degree of concentration-dependent licking of sucrose, likely attributable to learning related to prior postingestive experience. These results are consistent with prior findings in the literature, implicating the T1R2+3 heterodimer as the principal taste receptor for sweet-tasting ligands, and also provide support for the potential of postingestive experience to influence responding in the KO mice. In contrast, T1R2 KO and T1R3 KO mice displayed concentration-dependent licking responses to Polycose that tracked those of their WT controls and in some cases licked midrange concentrations more; the number of Polycose trials initiated overall did not differ between KO and WT mice. Thus, the T1R2 and T1R3 proteins are individually unnecessary for normal concentration-dependent licking of Polycose to be expressed in a brief-access test. Whether at least one of these T1R protein subunits is necessary for normal Polycose responsiveness remains untested. Alternatively, there may be a novel taste receptor(s) that mediates polysaccharide taste.

Taste impairment is a complication of Diabetes mellitus and some studies have shown this taste disorder in diabetes. Diabetes can decrease the ability of individuals to detect and recognize sweet, salty and bitter tastes. alpha-Gustducin is a transducin-like G-protein selectively expressed in 20 - 30% of taste receptor cells, which has been shown to be involved in bitter, sweet and umami taste responses. The present study was performed to explore the protein and mRNA expression of alpha-gustducin in the taste buds of diabetic and control rat circumvallate papillae. Our results showed that the positive expression of alpha-gustducin in diabetic rat taste bud cells is higher than that in normal controls as shown by both immunohistochemistry and RT-PCR. There may be some variant of bitter, sweet or umami taste transduction during diabetes and that taste transduction variant may be one cause of diabetic taste impairment.

Calcium is an essential nutrient that induces a distinctive taste quality, but the sensing mechanism of calcium in the tongue is poorly understood. A recent study linked calcium to T1R3 receptor. Here, we propose another system for calcium taste involving the extracellular calcium-sensing receptor (CaSR). This G protein-coupled receptor that responds to calcium and magnesium cations is involved in calcium homeostasis regulating parathyroid and kidney functions. In this study, CaSR was found in isolated taste buds from rats and mice. It was expressed in a subset of cells in circumvallate and foliate papillae, with fewer cells in the fungiform papillae. This is the first evidence in mammals that locates CaSR in gustatory tissue and provides the basis for better understanding not only calcium taste but also the taste of multiple CaSR agonists.

Summary Glucagon-like peptide-1 (GLP-1), a 30-amino-acid peptide hormone, is a typical peptide of the brain–gut axis and can affect the metabolism of various tissues and organs. GLP-1 is secreted by intestinal L cells in response to nutrient ingestion. Some studies have shown that taste signaling elements were co-expressed in enteroendocrine cells of the small intestine, and in particular by L-cells. The present study was performed to explore the protein and mRNA expression of GLP-1 in the taste buds of rat circumvallate papillae and to try to determine the significance of its secretion. GLP-1 immunoreactivity was observed in spindle-shaped taste bud cells, with positive cells displaying a characteristic distribution of reaction product that was confined to the cytosol. Reverse transcription polymerase chain reaction (RT-PCR) assay showed that GLP-1 mRNA was expressed in circumvallate papillae. The expression of GLP-1 suggests that it may play an important role in the taste stimulation of nutrients and gut hormone secretion.

Glucagon-like peptide-1 (GLP-1), released from gut endocrine L cells in response to glucose, regulates appetite, insulin secretion, and gut motility. How glucose given orally, but not systemically, induces GLP-1 secretion is unknown. We show that human duodenal L cells express sweet taste receptors, the taste G protein gustducin, and several other taste transduction elements. Mouse intestinal L cells also express alpha-gustducin. Ingestion of glucose by alpha-gustducin null mice revealed deficiencies in secretion of GLP-1 and the regulation of plasma insulin and glucose. Isolated small bowel and intestinal villi from alpha-gustducin null mice showed markedly defective GLP-1 secretion in response to glucose. The human L cell line NCI-H716 expresses alpha-gustducin, taste receptors, and several other taste signaling elements. GLP-1 release from NCI-H716 cells was promoted by sugars and the noncaloric sweetener sucralose, and blocked by the sweet receptor antagonist lactisole or siRNA for alpha-gustducin. We conclude that L cells of the gut "taste" glucose through the same mechanisms used by taste cells of the tongue. Modulating GLP-1 secretion in gut "taste cells" may provide an important treatment for obesity, diabetes and abnormal gut motility.