Search Results (98)

Sweet taste receptors (STRs) are class C G protein-coupled receptors (GPCRs) that function as heterodimers of TAS1R2 and TAS1R3. These receptors possess multiple binding sites and can be activated by a wide range of sweet-tasting compounds. Interestingly, TAS1R2 alone or even its extracellular domain-truncated form (TAS1R2-TMD), can act as a functional receptor. Previous studies demonstrated that the sweetener S819 and the sweet inhibitor amiloride act through the transmembrane domain (TMD) of TAS1R2; however, the molecular mechanisms underlying these ligand-specific effects remain unclear, largely due to the historical lack of experimentally determined full-length STR structures. Recent breakthroughs in cryo-EM structural determination of the full-length TAS1R2/TAS1R3 complex now offer an unprecedented opportunity to elucidate receptor activation mechanisms at atomic resolution. In this study, we investigated ligand-induced conformational dynamics of hTAS1R2-TMD using microsecond-scale molecular dynamics (MD) simulations on three systems: hTAS1R2-TMD/S819 (agonist-bound), hTAS1R2-TMD/amiloride (antagonist-bound), and hTAS1R2-TMD (apo). Comparative analyses revealed that agonist and antagonist binding distinctly modulate key structural switches, including the conserved ionic lock (E6.35-R3.50), which stabilizes the inactive state and disrupts upon activation. Notably, we identified a novel salt bridge (D7.32-R3.32) that forms preferentially in the active state, potentially serving as a unique molecular switch for TAS1R2. Additional analyses uncovered ligand-specific rearrangements in hydrogen-bonding and hydrophobic interaction networks. These results provide atomistic insights into how agonists and antagonists differentially modulate TAS1R2 activation and lay a structural foundation for designing novel sweeteners and taste modulators. Full article

Thermal processing is widely applied in food manufacturing to enhance flavor, but the mechanisms underlying taste transformation remain insufficiently understood. Rehmannia Radix, traditionally processed by steaming, undergoes a distinctive shift from bitterness to sweetness, serving as a representative model for flavor modulation during processing. In this study, sensory evaluation (n = 12), electronic tongue analysis, HPLC-based sugar and marker profiling across 17 batches, and molecular docking with representative human taste receptors were combined to investigate the mechanisms of taste transformation. The results showed that steaming markedly increased sweetness while reducing bitterness (p < 0.05). Chemical profiling revealed the hydrolysis of oligosaccharides into higher-sweetness monosaccharides (e.g., fructose (Fru) +15.99%, glucose (Glu) +8.90%) and substantial degradation of bitter iridoid glycosides (e.g., catalpol (Cat) −88%). In addition, the formation of 5-hydroxymethylfurfural (5-HMF) was identified as a processing marker. Molecular docking suggested that bitter glycosides in raw samples may interfere with sweet receptor activation and stimulate bitter receptors, whereas monosaccharide enrichment and Maillard products favored sweet receptor interactions, which may explain the observed sensory changes. Overall, these results clarify the chemical basis and receptor-level mechanisms of the bitterness-to-sweetness transition during steaming and identify markers useful for monitoring flavor changes in Rehmannia Radix. Full article

The rise in diabetes and obesity worldwide has created an urgent demand for low-sugar, nutrient-dense foods with appealing flavors. This study established an endogenous and “rapid validation–stable production” platform to enhance the flavor of edible tomato fruits by integrating two key technologies in the MicroTom cherry tomato: (1) TRV viral vector-mediated transient expression and (2) Agrobacterium-mediated stable genetic transformation. We employed the human sweet taste receptor TAS1R2 for in vitro functional validation and objectively demonstrated that tomato-derived recombinant thaumatin II exhibits receptor-binding activity equivalent to that of the native protein, overcoming the limitations of traditional sensory evaluation. Non-targeted metabolomic analysis (covering 1236 metabolites) confirmed that thaumatin II expression did not significantly alter the profiles of sugars, organic acids, or key flavor compounds in tomato fruits. This provides safety data supporting the development of “ready-to-eat sugar-substitute fruits.” Our strategy offers a solution and theoretical technical support for the development of low-sugar, high-nutrient foods. Full article

Background: Sweet taste adaptation, the decline in perceived sweetness with repeated exposure, may influence dietary behavior and differs across sweeteners. Low-calorie sweeteners (LCSs) such as sucralose strongly activate the T1R2+T1R3 receptor and are generally associated with greater adaptation than sugars, although this effect can be reduced with sweetener blends. Aim: We investigated whether habitual LCS consumption affects sweet taste perception and whether blending sucralose with small amounts of sugars attenuates adaptation using sensory tests in humans and in vivo calcium imaging in a rodent model. Methods: In study 1, habitual (HC; n = 39) and non-habitual (NHC; n = 42) LCS consumers rate sweetness of sucralose (0.6 mM), glucose (800 mM), fructose (475 mM), and blends with low glucose (111 mM) or fructose (45 mM) across repeated trials (1–10) using a generalized labeled magnitude scale. In study 2, a microfluidic-based intravital tongue imaging system was used to assess in vivo responses to sweet adaptation in genetically modified C57BL/6 mice (n = 8) expressing a calcium indicator in type II/III cells of taste buds. Results: Habitual LCS use was not associated with differences in sweetness perception or adaptation (all p-values > 0.6). Sucralose alone produced stronger adaptation than when blended with sugars in both humans (p-values < 0.002) and mice (p < 0.001). Glucose and fructose alone showed adaptation (relative decrease reached on final trial compared to the first trial: −27% ± 4% for glucose, −38% ± 5% for fructose, both p-values < 0.002) but to a lower degree compared with sucralose (−66% ± 5%). Conclusions: Sweetener composition, rather than habitual LCS use, drives sweet taste adaptation. Blending sucralose with small amounts of sugars reduces adaptation at both perceptual and cellular levels, providing mechanistic insights relevant to the formulation of LCS products. Full article

This manuscript provides an in-depth review of both artificial and natural sweeteners, including polyols and plant-derived alternatives, examining their sweetening potency, glycemic index, modes of action, and applications in the food sector. The rising demand for sugar substitutes, fueled by health concerns such as obesity and diabetes, has prompted significant research into low-calorie and non-nutritive sweeteners. This work categorizes sweeteners into synthetic options (such as aspartame, sucralose, saccharin) and naturally occurring ones (such as stevia, monk fruit, and polyols like sorbitol, xylitol, erythritol), focusing on physico-chemical characteristics, relative sweetness (ranging from 100 to 220,0000 times sweeter than sucrose), and glycemic index, important for their use in diabetes-friendly food products. The current manuscript examines how these sweeteners interact with taste receptors to induce sweetness perception without contributing significant calories. It also discusses their health implications and controversies and limitations regarding healthy and safety data, process feasibility, market application trends, environmental stability, and commercialization challenges. The review also addresses challenges in scaling production and ensuring the economic viability of plant-based sweeteners, offering a forward-looking perspective on their commercialization in the food industry. Full article

Low-calorie sweeteners (LCS) are widely utilized as sugar substitutes due to their intense sweetness, thermal stability, and applicability in weight management and diabetic-friendly products. However, increasing evidence has raised concerns about their potential long-term effects on metabolic health, glucose regulation, cardiovascular function, carcinogenicity, and gut microbiota composition. This review systematically evaluates the pharmacokinetics, metabolic effects, and associated health outcomes of major LCS. Mechanistically, LCS exert effects via sweet taste receptor-mediated pathways, altering glucose absorption, insulin secretion, and intracellular signaling cascades. Additionally, LCS influence gut microbiota composition, with certain agents promoting dysbiosis and glucose intolerance. While some findings support the metabolic benefits of selected LCS, others underscore potential risks, necessitating cautious interpretation. In conclusion, while LCS offer viable alternatives to sugar, their health effects are context-dependent and may vary across different sweeteners and populations. Long-term, high-quality clinical trials are essential to elucidate their safety and efficacy. Full article

This study examines the relationship between dietary patterns, specifically the Mediterranean diet (MD) and the Western diet (WD), and sensory perception among nursing students at the University of Valladolid, Spain. The study aims to understand how these dietary patterns affect taste sensitivity and preferences, contributing to the fields of nutrition and sensory science. Materials and Methods: A total of 41 students participated in this study, following ethical guidelines. Food-grade materials such as refined salt, sucrose, monosodium glutamate, water, and breadsticks were used in sensory assessments. The study involved structured sensory evaluations along with dietary habit questionnaires. Sensory tests were conducted to measure taste perception, and statistical analyses were performed using IBM SPSS Statistics 25.0, with descriptive statistics and correlation analysis. Results: The findings revealed significant differences in taste perception across diet adherence levels. Specifically, higher adherence to the MD was associated with a higher perceived intensity and enjoyment of saltiness and umami, while a higher adherence to the WD showed a preference for sweetness. Significant correlations were found between diet adherence and taste enjoyment, with stronger positive associations for saltiness and umami under the MD. Conclusions: This study emphasized the impact of dietary habits on taste perception. Adherence to the MD enhanced sensitivity to moderate taste intensities, while adherence to the WD resulted in decreased perception at lower concentrations and heightened sensory responses at higher intensities. These results suggest that long-term dietary patterns influence taste receptor adaptation, potentially affecting food choices and overall health. Full article

Sweet taste plays a pivotal role in human dietary behavior and metabolic regulation. With the increasing incidence of metabolic disorders linked to excessive sugar intake, the development and accurate evaluation of new sweeteners have become critical topics in food science and public health. However, the structural diversity of sweeteners and their complex interactions with sweet taste receptors present major challenges for standardized sweetness detection. This review offers a comprehensive and up-to-date overview of sweet taste transmission mechanisms and current detection methods. It outlines the classification and sensory characteristics of both conventional and emerging sweeteners, and explains the multi-level signaling pathway from receptor binding to neural encoding. Key detection techniques, including sensory evaluation, electronic tongues, and biosensors, are systematically compared in terms of their working principles, application scope, and limitations. Special emphasis is placed on advanced biosensing technologies utilizing receptor–ligand interactions and nanomaterials for highly sensitive and specific detection. Furthermore, an intelligent detection framework integrating molecular recognition, multi-source data fusion, and artificial intelligence is proposed. This interdisciplinary approach provides new insights and technical solutions to support precise sweetness evaluation and the future development of healthier food systems. Full article

Sweet sensing is a fundamental sensory experience that plays a critical role not only in food preference, reward and dietary behaviour but also in glucose metabolism. Sweet taste receptors (STRs), composed of a heterodimer of taste receptor type 1 member 2 (T1R2) and member 3 (T1R3), are now recognised as being widely distributed throughout the body, including the gastrointestinal tract. Preclinical studies suggest these receptors are central to nutrient and glucose sensing, detecting energy availability and triggering metabolic and behavioural responses to maintain energy balance. Both internal and external factors tightly regulate their signalling pathways, and dysfunction within these systems may contribute to the development of metabolic disorders such as obesity and type 2 diabetes (T2D). Functional magnetic resonance imaging (fMRI) has provided valuable insights into the neural mechanisms underlying sweet sensing by mapping brain responses to both lingual/oral and gastrointestinal sweet stimuli. This review highlights key findings from fMRI studies and explores how these neural responses are modulated by metabolic state and individual characteristics such as body mass index, habitual intake and metabolic health. By integrating current evidence, this review advances our understanding of the complex interplay between sweet sensing, brain responses, and health and identifies key gaps and directions for future research in nutritional neuroscience. Full article

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

The development of black tea quality is the outcome of the synergistic interaction between tea cultivars and the ecological environment of the production area, including factors such as climate, soil, and cultivation practices. Nevertheless, within a specific geographical region, systematic analysis of the environmental regulation mechanisms governing processing adaptability and quality formation among different cultivars remains insufficient. This study evaluated six Camellia sinensis cultivars from the Jingshan region of Hangzhou, China, integrating non-targeted metabolomics, sensory profiling, bioassays, and molecular docking to elucidate cultivar-specific quality attributes. Non-volatile metabolomics identified 84 metabolites linked to color and taste, including amino acids, catechins, flavonoid glycosides, and phenolic acids. Sensory and metabolite correlations revealed that amino acids enhanced brightness and imparted fresh-sweet flavors, while catechins contributed to bitterness and astringency. Specific metabolites, such as 4-hydroxybenzoyl glucose and feruloyl quinic acid, modulated color luminance. Volatile analysis identified 13 aroma-active compounds (OAV ≥ 1), with 1-octen-3-ol, phenylacetaldehyde, and linalool endowing JK with distinct floral-fruity notes. Molecular docking further demonstrated interactions between these volatiles and olfactory receptors (e.g., OR1A1 and OR2J2), providing mechanistic insights into aroma perception. These findings establish a robust link between cultivar-driven metabolic profiles in black tea, offering actionable criteria for cultivar selection and quality optimization in regional tea production. Full article

Background: In 2022, there were an estimated 20 million new cancer cases and 9.7 million deaths. The number of new cancer cases is expected to rise to over 35 million by 2050, marking a 75% increase from 2022 levels. Twenty to eighty-six percent of cancer patients suffer from taste disorders (TD), which are associated with an increased risk of malnutrition. Cachectic syndrome is linked to the presence and growth of tumors and leads to systemic inflammation. Synsepalum dulcificum is a plant whose berries contain miraculin, a glycoprotein that transforms sour tastes into sweet and can ameliorate TD. Objectives: To evaluate the effect of the regular intake of dried miracle berries (DMBs), a novel food containing miraculin, on biomarkers of inflammation and cachexia in malnourished patients with cancer and TD receiving systemic antineoplastic therapy. Methods: we conducted a triple-blind, randomized, placebo-controlled pilot clinical trial. Thirty-one patients with cancer of various etiologies who received chemotherapy were enrolled in this pilot study and divided into three groups. The first group received a tablet containing 150 mg of DMB (standard dose), the high-dose group received a tablet of 300 mg of DMB, and the third group received a tablet with 300 mg of the placebo for three months before each main meal. The plasma levels of several molecules associated with inflammation and cancer cachexia were measured using the X-MAP Luminex multiplexing platform. Results: We found decreased plasma levels of IFN-γ in the standard-dose group. In addition, our results suggest a downtrend of IL-1β levels in the three groups after three months of intervention (p = 0.093). Moreover, the three groups showed a reduction in tumor-derived molecule proteolysis-inducing factor/dermcidin (p = 0.021). It is important to highlight the positive correlation between IL-6 and IL-10 in the standard group, which suggests a better balance between proinflammatory and anti-inflammatory cytokines. Regardless of DMB consumption, soluble TNF receptor type II tended to decrease with treatment in patients who responded well to the antineoplastic treatment (p = 0.011). We did not find significant correlations between cytokines and sensory variables or dietary and nutritional status. Conclusions: Our results suggest that the regular consumption of a standard dose of DMB along with a systemic antineoplastic treatment could contribute to reducing inflammation and cachexia biomarkers in malnourished patients with cancer exhibiting TD. In this sense, nutritional support is crucial in the treatment of cancer cachexia. In our view, it should be considered a coadjuvant of therapeutics. Future studies on the molecular signaling pathways and specific mechanisms of action of bioactive compounds within food supplements, such as miraculin, will allow them to be used to target pathogenic mechanisms of cancer cachexia and malnutrition: NCT05486260. Full article