Search Results (29)

Background: Taste disorders in patients with type 2 diabetes mellitus (T2DM) have a negative impact on their quality of life and glycemic control, and treatment options are limited. Buzhong yiqi formula (BZYQF) improves T2DM symptoms but its effects on T2DM-induced taste disorders have not been sufficiently studied. Methods: Molecular docking was utilized to evaluate binding activity between the compounds in BZYQF and the sweet taste receptors (STRs). T2DM was induced in rats through the administration of high-fat diet and streptozotocin, and the rats were then treated with BZYQF for 8 weeks. Daily indicators and serum biochemical factors were monitored. Taste preferences for sweet, bitter, salty, and sour solutions were assessed using a two-bottle test. The morphology of lingual papillae and the numbers of taste buds were examined using HE staining. A high-glucose (HG) model of taste bud organoids was established to measure sucrose-evoked ATP release. The expression of signaling molecules in the sweet taste receptors (STRs) pathway was determined via RT-qPCR, Western blot, and immunofluorescence in lingual papillae and organoids. Results: A total of 508 compounds in BZYQF indicated good binding activity to T1R2, T1R3 or heterodimers of T1R2/T1R3, and 60 compounds had good binding activity to all three forms of STRs. BZYQF alleviated T2DM symptoms and improved taste perception for maltose (10 mM, 50 mM), quinine (0.03 mM, 0.1 mM), and citric acid (1 mM) solutions. BZYQF improved the morphological structure of lingual papillae and increased taste bud numbers in T2DM rats. BZYQF enhanced ATP release responses to sucrose solution in the taste bud organoids of the HG model. Gene expression determination showed that BZYQF upregulated the expression of signaling molecules in the STRs pathway (T1R2, T1R3, IP3R, α-gustducin, TRPM5) in the lingual papillae of the T2DM rats and in the taste bud organoids of the HG model. Conclusions: BZYQF alleviates T2DM-induced taste disorders by increasing the numbers of taste buds and upregulating STR signaling molecules, in which various compounds, especially flavonoids, exhibit a synergistic effect. Full article

Background/Objectives: Sweet taste receptor TAS1R2 is expressed in skeletal muscle, yet its role in muscle metabolism remains poorly understood. Methods: Here, we leverage the BXD recombinant inbred mouse panel and Tas1r2 whole-body knockout (bKO) models to investigate the transcriptional impact of Tas1r2 deficiency on skeletal muscle function. Results: A gene network analysis revealed significant overlap in transcriptomic signatures between BXD strains with low Tas1r2 expression (BXD L_Tas1r2) and bKO muscle, particularly in pathways regulating oxidative phosphorylation, cytoplasmic ribosome function, and proteostasis. Notably, Tas1r2 expression negatively correlated with genes involved in fatty acid metabolism, suggesting its role in lipid utilization. Under high-fat diet (HFD) conditions, BXD_HFD L_Tas1r2 mice exhibited further enrichment in pathways linked to proteasome degradation, oxidative stress, and interleukin signaling, amplifying the transcriptomic convergence with bKO models. Key transcription factors (Mlxipl, Nfic, Rxrb) exhibited altered regulatory patterns under dietary stress, indicating that TAS1R2 influences metabolic adaptability through transcriptional reprogramming. Conclusions: Given that human TAS1R2 variants rarely result in complete loss of function (LOF), the BXD panel provides an effective dose-dependent model to bridge the gap between knockout phenotypes and human SNP carriers. Our findings establish TAS1R2 as a metabolic regulator in skeletal muscle and highlight the utility of genetically diverse mouse populations in dissecting gene-diet interactions relevant to human metabolic diseases. Full article

Background: Obesity, mainly visceral obesity, causes a low-grade of chronic inflammation (meta-inflammation), associated with comorbidities such as type 2 diabetes, cardiovascular diseases, and certain cancers. Precision Nutrition aims to understand the bidirectional crosstalk between the genome and diet to improve human health. Additionally, by leveraging individual data, Precision Nutrition seeks to predict how people will respond to specific foods or dietary patterns, with the ultimate goal of providing personalized nutritional recommendations tailored to their unique needs and lifestyle factors, including poor dietary habits (e.g., high intake of sugar or saturated fatty acids, alcohol consumption, etc.) and sedentary habits, exacerbate obesity in genetically predisposed individuals. Genetic, metabolic, and environmental factors can play a crucial role during obesity. Objective: To investigate the effects of genetic variability in sweet taste receptors and their downstream signaling pathways in the gut–brain axis on anthropometry, biochemistry, and lifestyle variables. Methods: A sample of 676 volunteers (mean age of 42.22 ± 12 years, ranging from 18 to 73 years) from the database of the GENYAL platform for nutritional trials at the IMDEA Food Institute were included in this study. We present a first-in-class genetic chip, Glucosensing, designed to interrogate 25 single-nucleotide polymorphisms (SNPs) located in genes encoding sweet taste receptors and components of downstream signaling pathways. These include elements of the gut–brain axis and its associated metabolic networks, enabling a comprehensive analysis of individual variability in sweet taste perception and metabolic responses. Results: Several significant associations were found after correction for multiple comparisons, representing potential targets for personalized interventions. Full article

Background/Objectives: Dietary glucose is transported across the intestinal absorptive cell into the systemic circulation by the apically located Na⁺-dependent glucose transporter 1 (SGLT1, SLC5A1) and basally residing Na⁺-independent glucose transporter 2 (GLUT2, SLC2A2). Whilst recent experimental evidence has shown that sensing of sweet compounds by the gut-expressed sweet taste receptor T1R2–T1R3 and glucagon-like peptide-2 receptor signalling are components of the pathway controlling SGLT1 expression, little is known about the mechanisms involved in the regulation of GLUT2. In this study, we tested the hypothesis that T1R2–T1R3 and its downstream signalling pathway participate in the regulation of intestinal GLUT2. Methods: We used in vivo and in vitro approaches employing a weaning pig model, a heterologous expression assay, and knockout mice for elucidating the regulation of GLUT2 by luminal sugars. Results: A plant-based sweetener formulation included in piglets’ diet led to a marked increase in GLUT2 expression in piglets’ intestine, compared to controls. The sweeteners that do not activate pig T1R2–T1R3 failed to upregulate GLUT2. There was a significant increase in GLUT2 expression when the sweetener sucralose, which activates T1R2–T1R3, was included in the drinking water of wild-type mice. However, in knockout mice, in which the genes for the sweet receptor subunit T1R3 and the associated G-protein gustducin were deleted, there was no upregulation of GLUT2 expression in response to sucralose supplementation. There was a notable increase in GLUT2 expression in wild-type mice fed a high-carbohydrate diet compared to when maintained on a low-carbohydrate diet. However, in GLP-2 receptor knockout mice kept on the high-carbohydrate diet, there was no enhancement in GLUT2 expression. Conclusions: The experimental evidence suggests that luminal sweet sensing via T1R2–T1R3 and the enteroendocrine-derived GLP-2 are constituents of the regulatory pathway controlling GLUT2 expression. Full article

Background/Objectives: Studies have hypothesised that single-nucleotide polymorphisms (SNPs) in the TAS1R2 and TAS1R3 genes may alter sweet compound detection and eating habits, thereby increasing the risk of obesity. This in vitro study aims to measure the impact of human TAS1R2/TAS1R3 polymorphisms, some of which are thought to be involved in obesity, on the response of the sweet taste receptor to various sweeteners. It also aims to identify new SNPs in an obese population associated with a decrease in or loss of TAS1R2/TAS1R3 function. Methods: First, the effects of 12 human TAS1R2-SNPs and 16 human TAS1R3-SNPs, previously identified in the literature, on the response of the sweet taste receptor stimulated by 12 sweeteners were investigated using functional cellular assays. Second, a total of 162 blood samples were collected from an obese population (BMI between 25 and 35 kg/m²) involved in the SWEET project. The TaqMan method for SNP genotyping was carried out using DNA extracted from blood samples to identify new SNPs and predict possible/probable TAS1R2/TAS1R3 loss of function. Results: Although certain human TAS1R2/TAS1R3 SNPs showed reduced receptor response, they were not associated with particular phenotypes. Seven SNPs were predicted to severely impair the human TAS1R2/TAS1R3 response to sweeteners. Conclusions: Although some TAS1R2- and TAS1R3-SNPs have previously been associated with obesity, our cellular results do not confirm this association and reinforce the hypothesis, put forward by other researchers, that sweet taste perception and sugar consumption are governed by factors other than the TAS1R2 and TAS1R3 genes. Full article

Background: Sweet taste is partly modified by genetics. The rs35874116 single-nucleotide polymorphism (SNP) in taste receptor type 1 member 2 (TAS1R2) reduces the availability of a G protein-coupled receptor (GPCR), which binds to ‘sweet’ molecules. This might alter sweet taste perception, diet choices, and health outcomes. However, these findings, and other genes and pathways involved in sweet taste are yet to be identified. Therefore, a candidate gene study on TAS1R2 and a genome-wide association study (GWAS) exploring these outcomes were performed. Methods: TAS1R2 rs35874116, sweet perception, liking, diet, and health were investigated in two age- and sex-matched European cohorts (UK, n = 50/Italy, n = 235). Linear models were used to explore associations. The GWAS was performed with 2555 Italian participants. Associations with sweet food liking, food adventurousness (FA), reward dependence (RD), and health were explored. Results: The wildtype of TAS1R2 was associated with increased sweet taste and food liking (p = 0.049, β = 0.62, p = 0.038, β = 0.45), increased fibre consumption (p = 0.006, β = 7.95), and decreased HDL cholesterol (p = 0.025, β = −3.56). The GWAS identified rs58931966 in the regulator of G-protein signalling 9 (RGS9) gene. The minor allele was associated with decreased sweet food liking (p = 7.05 × 10 – 9, β = 0.3), a higher BMI (p = 0.007, β = 0.391), serum glucose (p = 0.013, β = 1.211), lower FA (p = 0.049, β = −0.065), and RD (p = 0.011, β = −3.840). Discussion: The TAS1R2 results show that taste receptor variations are associated with preference, diet, and health-related outcomes. TAS1R2 not reaching significance in the GWAS shows that sweet food liking is modified by pathways besides taste reception. RSG9 is expressed in the striatum, which is involved in the mesolimbic reward pathway, which is activated by sweet taste. RGS9 rs58931966 may moderate dopaminergic signalling in response to sweet foods via the negative regulation of G-protein signalling. This might explain why the minor allele was associated with reduced RD. The lower FA might decrease preference for bitter-tasting vegetables, which could explain the higher BMI and serum glucose. The FA and RD results provide evidence that food choice depends on psychological/biological interplay. These results show that sweet taste is modified by multiple pathways and genes, and variations can modify taste, diet, and health outcomes. Full article

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

Revealing the genetic background and phenotypes (phenome) of food selection and food preferences is a key factor to developing personalized nutrition in contemporary precision medicine and healthy lifestyles. Food choice in humans has multiple determinants, with complex interactions and the integration of genetic, physiological, psychological and sociocultural factors. Food intake involves ingestion, comprising an initiation phase, a termination/satiation phase and a interingestive period, which are under the genetic control of gastrointestinal neuroendocrine hormones, including cholecystokinin, leptin, ghrelin and FTO gene, contributing to obesity. Taste modalities are motivational priorities in food choices. The genomics of taste perception and preferences reveal genetic polymorphisms and genetic variations in taste receptors for bitter, sweet, umami, salty, and sour tastes and oleogustus. The integrated multisensory olfactory–gustatory perception, defined as flavor, is modulated by visual, auditory, tactile, and cognitive influences. Dopaminergic activation is crucial for the hedonic principle of ingesting food. The possibility of organisms sending signals to the brain in case of metabolic deficits, which gives rise to specific taste eagerness, is discussed. Based on this aspect, the concept of instinctive nutrition is formulated. Full article

Background and objectives: Several factors may account for food behavior, including common genetic variation. Robust evidence shows that specific single-nucleotide polymorphisms (SNPs) are involved in palatability phenotypes. Considering the limited knowledge of these associations in the context of admixed groups, like the Brazilian population, we aimed to investigate associations of SNPs in the TAS1R and TAS2R taste receptor gene families with diet quality. Methods: A sample of 901 individuals ≥ 12 years old from the general population, categorized into age groups (adolescents, adults, and elderly), was interviewed in the Health Survey of Sao Paulo (ISA-Capital). Data on socioeconomic, demographic, and health characteristics were collected, including dietary information from two 24 h recalls in two nonconsecutive days and blood samples. The 24 h recalls were analyzed using the Revised Brazilian Healthy Eating Index (BHEI-R), comprising 12 components referring to food groups, nutrients, and calories from saturated fats, alcohol, and added sugar. Blood samples were genotyped for 255 SNPs in the TAS2R gene family (related to bitterness) and 73 SNPs in the TAS1R (related to sweetness and umaminess). BHEI-R was normally inversed transformed (invBHEIR). After data cleaning and quality control procedures, genotype and phenotype data of 637 individuals were made available for association analysis with invBHEI-R using linear models adjusted for age, age2, age × sex, sex, BMI, and the two first principal components of ancestry. Genetic taste scores (GTSs) were derived from the significant SNPs of each gene family and tested for associations. Analysis was performed with the software R version 4.0.2 using a significance level of 0.05. Results: There were 31 SNPs of TAS2R genes and four SNPs of TAS1R genes significantly associated with BHEI-R (p < 0.05). GTSs were positively associated, and their use increased the model’s performance, especially with TAS2R SNPs (r² rose from 0.135 to 0.188). Conversely, the estimated effect of the TAS1R score on BHEI-R was 2.02 higher than the TAS2R one. Discussion: Our results show potential genetic influences on diet quality by applying genetic taste scores. Unraveling associations between SNPs and food intake might help guide public policies towards healthier food behavior considering genetic differences, i.e., personalized nutrition. Full article

There is wide variation in how individuals perceive the chemosensory attributes of liquid formulations of ibuprofen, encompassing both adults and children. To understand personal variation in the taste and chemesthesis properties of this medicine, and how to measure it, our first scientific strategy centered on utilizing trained adult panelists, due to the complex and time-consuming psychophysical tasks needed at this initial stage. We conducted a double-blind cohort study in which panelists underwent whole-genome-wide genotyping and psychophysically evaluated an over-the-counter pediatric medicine containing ibuprofen. Associations between sensory phenotypes and genetic variation near/within irritant and taste receptor genes were determined. Panelists who experienced the urge to cough or throat sensations found the medicine less palatable and sweet, and more irritating. Perceptions varied with genetic ancestry; panelists of African genetic ancestry had fewer chemesthetic sensations, rating the medicine sweeter, less irritating, and more palatable than did those of European genetic ancestry. We discovered a novel association between TRPA1 rs11988795 and tingling sensations, independent of ancestry. We also determined for the first time that just tasting the medicine allowed predictions of perceptions after swallowing, simplifying future psychophysical studies on diverse populations of different age groups needed to understand genetic, cultural–dietary, and epigenetic factors that influence individual perceptions of palatability and, in turn, adherence and the risk of accidental ingestion. Full article

The expression of canonical chemosensory receptors of the tongue, such as the heteromeric sweet taste (TAS1R2/TAS1R3) and umami taste (TAS1R1/TAS1R3) receptors, has been demonstrated in many extra-oral cells and tissues. Gene expression studies have revealed transcripts for all TAS1 and metabotropic glutamate (mGlu) receptors in different types of immune cells, where they are involved, for example, in the chemotaxis of human neutrophils and the protection of T cells from activation-induced cell death. Like other class-C G protein-coupling receptors (GPCRs), TAS1Rs and mGlu receptors form heteromers within their families. Since mGlu receptors and TAS1R1/TAS1R3 share the same ligand, monosodium glutamate (MSG), we hypothesized their hitherto unknown heteromerization across receptor families in leukocytes. Here we show, by means of immunocytochemistry and co-IP/Western analysis, that across class-C GPCR families, mGlu₂ and TAS1R3 co-localize and heterodimerize in blood leukocytes. Expressing the recombinant receptors in HEK-293 cells, we validated their heterodimerization by bioluminescence resonance energy transfer. We demonstrate MSG-induced, mGlu₂/TAS1R3 heteromer-dependent gain-of-function and pertussis toxin-sensitive signaling in luminescence assays. Notably, we show that mGlu₂/TAS1R3 is necessary and sufficient for MSG-induced facilitation of N-formyl-methionyl-leucyl-phenylalanine-stimulated IL-8 secretion in neutrophils, using receptor-specific antagonists. In summary, our results demonstrate mGlu₂/TAS1R3 heterodimerization in leukocytes, suggesting cellular function-tailored chemoreceptor combinations to modulate cellular immune responses. Full article

Taste perception is a well-documented driving force in food selection, with variations in, e.g., taste receptor encoding and glucose transporter genes conferring differences in taste sensitivity and food intake. We explored the impact of maternal innate driving forces on sweet taste preference and intake and assessed whether their children differed in their intake of sweet foods or traits related to sweet intake. A total of 133 single nucleotide polymorphisms (SNPs) in genes reported to associate with eating preferences were sequenced from saliva-DNA from 187 mother-and-child pairs. Preference and intake of sweet-, bitter-, sour-, and umami-tasting foods were estimated from questionnaires. A total of 32 SNP variants associated with a preference for sweet taste or intake at a p-value < 0.05 in additive, dominant major, or dominant minor allele models, with two passing corrections for multiple testing (q < 0.05). These were rs7513755 in the TAS1R2 gene and rs34162196 in the OR10G3 gene. Having the T allele of rs34162196 was associated with higher sweet intake in mothers and their children, along with a higher BMI in mothers. Having the G allele of rs7513755 was associated with a higher preference for sweets in the mothers. The rs34162196 might be a candidate for a genetic score for sweet intake to complement self-reported intakes. Full article

This study investigated the effect of dietary flavour supplements on the preference, feed efficiency and expression of the sweet taste receptor family 1 members 2 and 3 (T1R2 + T1R3), and sodium-glucose linked transporter 1 (SGLT1) genes in the lambs’ small intestines. Eight, five-month-old, Israeli crossbred Assaf lambs were offered 16 different non-nutritive commercial flavours in rolled barley and ground corn. Capsicum and sucram were the most preferred non-aroma flavours (p = 0.020), while milky (p < 0.001) was the most preferred powder-aroma flavour. For the metabolic and relative gene expression study, eight lambs were randomly assigned to either sucram, capsicum, a mix containing sucram and capsicum at 1:1 ratio or no flavour for control in a 4 × 2 cross-over design. The total collection of urine (females only), faeces and refusals was carried out, and T1R2, T1R3 and SGLT1 relative gene expression evaluated from the proximal jejunum biopsies. Flavour had no significant effect on the feed intake (p = 0.934), but capsicum increased the average daily weight gain per metabolic body weight (p = 0.049). The T1R3 gene was expressed highest in the mix treatment (1.7; p = 0.005). Collectively, our findings indicate that flavours can be used to motivate feed acceptance and improve the weight gain in lambs. Full article

Individual differences in sweet taste sensitivity can affect dietary preferences as well as nutritional status. Despite the lack of consensus, it is believed that sweet taste is impacted by genetic and environmental variables. Here we determined the effect of well-established factors influencing the general taste variability, such as gender and fungiform papillae density, specific genetic variants (SNPs of TAS1R2 and TAS1R3 receptors genes), and non-specific genetic factors (PROP phenotype and genotype), on the threshold and suprathreshold sweet taste sensitivity. Suprathreshold measurements showed that the sweet taste response increased in a dose-dependent manner, and this was related to PROP phenotype, gender, rs35874116 SNP in the TAS1R2 gene, and rs307355 SNP in the TAS1R3 gene. The threshold values and density of fungiform papillae exhibited a strong correlation, and both varied according to PROP phenotype. Our data confirm the role of PROP taste status in the sweet perception related to fungiform papilla density, show a higher sweet sensitivity in females who had lower BMI than males, and demonstrate for the first time the involvement of the rs35874116 SNP of TAS1R2 in the sweet taste sensitivity of normal weight subjects with body mass index (BMI) ranging from 20.2 to 24.8 kg/m². These results may have an important impact on nutrition and health mostly in subjects with low taste ability for sweets and thus with high vulnerability to developing obesity or metabolic disease. Full article

Sweet taste, a proxy for sugar-derived calories, is an important driver of food intake, and animals have evolved robust molecular and cellular machinery for sweet taste signaling. The overconsumption of sugar-derived calories is a major driver of obesity and other metabolic diseases. A fine-grained appreciation of the dynamic regulation of sweet taste signaling mechanisms will be required for designing novel noncaloric sweeteners with better hedonic and metabolic profiles and improved consumer acceptance. Sweet taste receptor cells express at least two signaling pathways, one mediated by a heterodimeric G-protein coupled receptor encoded by taste 1 receptor members 2 and 3 (TAS1R2 + TAS1R3) genes and another by glucose transporters and the ATP-gated potassium (K_ATP) channel. Despite these important discoveries, we do not fully understand the mechanisms regulating sweet taste signaling. We will introduce the core components of the above sweet taste signaling pathways and the rationale for having multiple pathways for detecting sweet tastants. We will then highlight the roles of key regulators of the sweet taste signaling pathways, including downstream signal transduction pathway components expressed in sweet taste receptor cells and hormones and other signaling molecules such as leptin and endocannabinoids. Full article