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The context for this review is the rapid increase in the use of non-nutritive sweeteners (NNSs) instead of sugar in foods and beverages, a situation so prevalent in some countries that consumers are finding it increasingly challenging to access foods without NNSs. The benefits of consuming NNSs on obesity and diabetes are now being questioned, and studies have shown that they may exert physiological activities, sometimes independently of sweet taste receptor stimulation. Few studies, limited mainly to North American and European countries, have described the consumption of NNSs by pregnant or lactating women and infants. Most focus on beverages rather than foods, but all agree that consumption levels have increased dramatically. Although some studies report a negative impact of NNSs on the risk of preterm birth, increased birth weight and decreased gestational age, the level of evidence is low. Several studies have also reported increased weight gain in infancy, associated with maternal NNS intake. Interestingly, several NNSs have been detected in amniotic fluid and breast milk, usually (but not always) at concentrations below their established detection limit in humans. Unfortunately, the impact of chronic exposure of the fetus/infant to low levels of multiple NNSs is unknown. In conclusion, there is a stark contrast between the galloping increase in the consumption of NNSs and the small number of studies evaluating their impact in at-risk groups such as pregnant and lactating women and infants. Clearly, more studies are needed, especially in Latin America and Asia, to fill these gaps and update recommendations.
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The chemical senses of olfaction and taste are well developed in fish and play a vital role in its various activities such as navigation, mate recognition, and food detection. The small teleost fish Astyanax mexicanus consists of interfertile river-dwelling and cave-dwelling populations, referred to as "surface fish" and "cavefish" respectively. An important anatomical feature of cavefish is the lack of eyes leading them to be referred to as blind fish and suggesting an enhanced functional role for other senses such as taste. In this study, we characterize the expression of bitter taste receptors (T2Rs or Tas2Rs) in A. mexicanus and investigate their functionality in a heterologous expression system. The genome database of A. mexicanus (ensemble and NCBI) showed 7 Tas2Rs, among these Tas2R1, Tas2R3, Tas2R4, and Tas2R114 are well characterized in humans and mice but not in A. mexicanus. Therefore, the 4 Tas2Rs were selected for further analysis and their expression in A. mexicanus was confirmed by in situ hybridization and RT-PCR in early developmental stages. These Tas2Rs are expressed in various oral and extraoral organs (liver, fins, jaws, and gills) in A. mexicanus, and Tas2R1 has maximum expression and is localized throughout the fish body. Using the heterologous expression of A. mexicanus T2Rs in HEK293T cells coupled with cell-based calcium mobilization assays, we show that A. mexicanus T2Rs are activated by commonly used fish food and known bitter agonists, including quinine. This study provides novel insights into the extraoral expression of T2Rs in A. mexicanus and suggests their importance in extraoral food detection.
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Metabolic syndrome is a multifactorial disorder originating from central obesity through a high caloric intake and a sedentary lifestyle. Metabolic syndrome increases the risk of type 2 diabetes (T2D) disease, converting it to one of the costliest chronic diseases, which reduces life quality. A strategy proposed by the food industry to reduce this problem is the generation of low-caloric products using sweeteners, which are compounds that can substitute sucrose, given their sweet taste. For many years, it was assumed that sweeteners did not have a relevant interaction in metabolism. However, recent studies have demonstrated that sweeteners interact either with metabolism or with gut microbiota, in which sweet-taste receptors play an essential role. This review presents an overview of the industrial application of most commonly consumed sweeteners. In addition, the interaction of sweeteners within the body, including their absorption, distribution, metabolism, gut microbiota metabolism, and excretion is also reviewed. Furthermore, the complex relationship between metabolic syndrome and sweeteners is also discussed, presenting results from in vivo and clinical trials. Findings from this review indicate that, in order to formulate sugar-free or noncaloric food products for the metabolic syndrome market, several factors need to be considered, including the dose, proportions, human metabolism, and interaction of sweeteners with gut microbiota and sweet-taste receptors. More clinical studies, including the metabolic syndrome, are needed to better understand the interaction of sweeteners with the human body, as well as their possible effect on the generation of dysbiosis.
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Microbioma Gastrointestinal , Síndrome Metabólica/prevenção & controle , Receptores Acoplados a Proteínas G/metabolismo , Edulcorantes/química , Edulcorantes/classificação , Edulcorantes/metabolismo , Diabetes Mellitus Tipo 2/prevenção & controle , Disbiose/metabolismo , Humanos , Síndrome Metabólica/dietoterapia , Obesidade/prevenção & controle , Edulcorantes/uso terapêuticoRESUMO
BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP), and aspirin-exacerbated respiratory disease (AERD) have varying levels of inflammation and disease severity. Solitary chemosensory cells (SCCs) are enriched in nasal polyps, are the primary source of interleukin 25 (IL-25) in upper airways, leading to type 2 inflammation, and are activated by bitter-tasting denatonium benzoate (DB). Thus, we sought to evaluate DB taste perception at a range of concentrations in order to identify 1 that most differentiates CRS subgroups from controls. METHODS: CRSsNP (n = 25), CRSwNP (n = 26), and AERD (n = 27) patients as well as controls (n = 25) tasted 6 DB concentrations in a fixed, random order, rating on a category scale of 0 (no intensity) to 12 (extremely intense). Sinonasal epithelial cultures were treated with and without denatonium and analyzed for IL-25 via flow cytometry. RESULTS: CRSsNP patients rated DB as significantly less intense than did controls at all concentrations: 5.62 × 10-9 M, 1.00 × 10-8 M, 1.78 × 10-8 M, 3.16 × 10-8 M, 5.62 × 10-8 M, and 1.00 × 10-7 M (all p < 0.0083). CRSwNP patients did not show significant differences from controls. AERD patients rated DB as significantly more intense than did controls at concentrations of 1.00 × 10-8 M and 3.16 × 10-8 M (p < 0.0083). In vitro data demonstrated significant increase in IL-25-positive cells after denatonium stimulation (n = 5), compared to control (n = 5) (p = 0.012). CONCLUSION: Our findings link in vitro DB stimulation of sinonasal tissue with increased IL-25 and show differential DB taste perception in CRS subgroups relative to the control group, with CRSsNP being hyposensitive and AERD being hypersensitive. We propose a concentration of 3.16 × 10-8 M for future study of clinical utility.
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Pólipos Nasais , Rinite , Sinusite , Doença Crônica , Humanos , Compostos de Amônio Quaternário , Percepção GustatóriaRESUMO
BACKGROUND: Bitter and sweet taste receptors are present in the human upper airway, where they have roles in innate immunity. Previous studies have shown that 1 of the 25 bitter receptors, TAS2R38, responds to specific bacterial signaling molecules and evokes 1 type of a defense response in the upper airway, whereas ligands of sweet receptors suppress other types of defense responses. METHODS: We examined whether other bitter taste receptors might also be involved in innate immunity by using sensory responses to bitter compounds that are not ligands of TAS2R38 (quinine and denatonium benzoate) to assess the sensitivity of other bitter receptors in chronic rhinosinusitis (CRS) patients. CRS patients with (n = 426) and without (n = 226) nasal polyps and controls (n = 356) rated the intensity of quinine, denatonium benzoate, phenylthiocarbamide (PTC; a ligand for TAS2R38), sucrose, and salt. RESULTS: CRS patients rated the bitter compounds denatonium benzoate and quinine as less intense and sucrose as more intense than did controls (false discovery rate [FDR] <0.05) and CRS patients and controls did not differ in their ratings of salt (FDR >0.05). PTC bitter taste intensity differed between patient and control groups but were less marked than those previously reported. Though differences were statistically significant, overall effect sizes were small. CONCLUSION: CRS patients report bitter stimuli as less intense but sweet stimuli as more intense than do control subjects. We speculate that taste responses may reflect the competence of sinonasal innate immunity mediated by taste receptor function, and thus a taste test may have potential for clinical utility in CRS patients.
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Pólipos Nasais , Sinusite , Humanos , Receptores Acoplados a Proteínas G , Paladar , Percepção GustatóriaRESUMO
Taste changes caused by the use of platinum drugs have been described. However, few studies qualify the impaired tastes and whether these changes are derived exclusively from chemotherapy (QTx). AIMS: Evaluation of changes in sweet, sour, salty, bitter, and umami tastes in patients receiving QTx with platinum drugs was the aim of this study. METHODS: A total of 43 subjects, 21 from the study group and 22 from the control, were studied in two time periods, one before the start of QTx (T0) and another after two cycles of QTx (T1). The usual dietary intake, body mass index (BMI), handgrip strength and fatigue (through the fatigue pictogram) were evaluated to characterize the group studied. Taste Strips tests were performed for all 4 tastes and umami was studied by comparing Likert's scale using monosodium glutamate (GMS) food. Statistical analysis was performed using repeated measures (ANOVA), mixed model, with significance level p≤0.05. RESULTS: Salty and sour were the most affected tastes in the study group (p = 0.001 and 0.05); as well as the ionotropic receptors (p = 0.02) responsible for identifying these tastes. There was a difference between the times for BMI, dynamometry and impact in daily activities, by the fatigue pictogram (p = 0.008, 0.009 and 0.006 respectively). CONCLUSION: These findings suggest an important role in altering taste recognition, mainly in salty and sour tastes, identified by ionotropic receptors, which seems to be related to dietary changes. QTx has demonstrated a contribution to impairment of functionality and fatigue.
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Antineoplásicos/efeitos adversos , Compostos de Platina/efeitos adversos , Distúrbios do Paladar/induzido quimicamente , Paladar/efeitos dos fármacos , Adulto , Idoso , Carboplatina/efeitos adversos , Estudos de Casos e Controles , Cisplatino/efeitos adversos , Disgeusia/induzido quimicamente , Disgeusia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/fisiopatologia , Oxaliplatina/efeitos adversos , Receptores Ionotrópicos de Glutamato/efeitos dos fármacos , Receptores Ionotrópicos de Glutamato/fisiologia , Receptores de Glutamato Metabotrópico/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/fisiologia , Paladar/fisiologia , Distúrbios do Paladar/fisiopatologiaRESUMO
It is difficult to know if the cause for obesity is the type of sweetener, high fat (HF) content, or the combination of sweetener and fat. The purpose of the present work was to study different types of sweeteners; in particular, steviol glycosides (SG), glucose, fructose, sucrose, brown sugar, honey, SG + sucrose (SV), and sucralose on the functionality of the adipocyte. Male Wistar rats were fed for four months with different sweeteners or sweetener with HF added. Taste receptors T1R2 and T1R3 were differentially expressed in the tongue and intestine by sweeteners and HF. The combination of fat and sweetener showed an additive effect on circulating levels of GIP and GLP-1 except for honey, SG, and brown sugar. In adipose tissue, sucrose and sucralose stimulated TLR4, and c-Jun N-terminal (JNK). The combination of HF with sweeteners increased NFκB, with the exception of SG and honey. Honey kept the insulin signaling pathway active and the smallest adipocytes in white (WAT) and brown (BAT) adipose tissue and the highest expression of adiponectin, PPARγ, and UCP-1 in BAT. The addition of HF reduced mitochondrial branched-chain amino transferase (BCAT2) branched-chain keto acid dehydrogenase E1 (BCKDH) and increased branched chain amino acids (BCAA) levels by sucrose and sucralose. Our data suggests that the consumption of particular honey maintained functional adipocytes despite the consumption of a HF diet.
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Tecido Adiposo/efeitos dos fármacos , Dieta Hiperlipídica , Açúcares da Dieta/farmacologia , Insulina/sangue , Edulcorantes/farmacologia , Papilas Gustativas/metabolismo , Receptor 4 Toll-Like/metabolismo , 3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)/sangue , Adiponectina/sangue , Tecido Adiposo/citologia , Animais , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/farmacologia , Mel , Incretinas/sangue , Inflamação/metabolismo , Masculino , Proteínas de Membrana Transportadoras/sangue , Proteínas Mitocondriais , Transportadores de Ácidos Monocarboxílicos , NF-kappa B/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , PPAR gama/sangue , Ratos Wistar , Proteínas Carreadoras de Solutos , Stevia , Sacarose/análogos & derivados , Sacarose/farmacologia , Paladar , Transaminases , Proteína Desacopladora 1/sangueRESUMO
Most sweeteners are plagued with unwanted unpleasant aftertastes. Here we examined the possibility that one of the main reasons for this is the similarity of sweet and umami receptors. We performed docking calculations on models of sweet and umami receptors using as template the recently determined solid state structure of the first taste receptor, the medaka fish T1R2-T1R3 receptor. Our results show convincingly that sweeteners can be recognized also by the T1R1-T1R3 umami receptor, owing to the similarity of its architecture to that of the sweet receptor. We hypothesize that the T1R1-T1R3 receptor plays a key role in modulating the quality of sweet tastants, hinting at a simple explanation of their aftertaste. The prevailing ideas on taste coding favor strict labeling of taste cells, which would exclude that umami receptors can recognize other taste sensations. If some cross-talk based on the combinatorial model of taste is accepted, some sweet ligands can exert a bitter sensation. However, even if cross-talk is not admitted, direct stimulation of the umami receptor is bound to cause an aftertaste incompatible with good sweet quality.
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Abstract 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.
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BACKGROUND: Sinonasal bitter taste receptors (T2Rs) contribute to upper airway innate immunity and correlate with chronic rhinosinusitis (CRS) clinical outcomes. A subset of T2Rs expressed on sinonasal solitary chemosensory cells (SCCs) are activated by denatonium, resulting in a calcium-mediated secretion of bactericidal antimicrobial peptides (AMPs) in neighboring ciliated epithelial cells. We hypothesized that there is patient variability in the amount of bacterial killing induced by different concentrations of denatonium and that the differences correlate with CRS clinical outcomes. METHODS: Bacterial growth inhibition was quantified after mixing bacteria with airway surface liquid (ASL) collected from denatonium-stimulated sinonasal air-liquid interface (ALI) cultures. Patient ASL bacterial killing at 0.1 mM denatonium and baseline characteristics and sinus surgery outcomes were compared between these populations. RESULTS: There is variability in the degree of denatonium-induced bacterial killing between patients. In CRS with nasal polyps (CRSwNP), patients with increased bacterial killing after stimulation with low levels of denatonium undergo significantly more functional endoscopic sinus surgeries (FESSs) (p = 0.037) and have worse 6-month post-FESS 22-item Sino-Nasal Outcome Test (SNOT-22) scores (p = 0.012). CONCLUSION: Bacterial killing after stimulation with low levels of denatonium correlates with number of prior FESS and postoperative SNOT-22 scores in CRSwNP. Some symptoms of CRS in patients with hyperresponsiveness to low levels of denatonium may be due to increased airway immune activity or inherent disease severity.