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A diferença da percepção álgica entre homens e mulheres é, há muito, conhecida e documentada na literatura. Sabe-se também que a sensibilidade feminina varia durante o ciclo menstrual, o que levou à hipótese de que os hormônios ovarianos poderiam estar envolvidosnesse processo. Assim, este estudo teve como objetivo investigar os limiares de sensibilidade somestésica (térmica, dolorosa, tátil, vibratória e elétrica), gustativa e olfativa durante o ciclo menstrual de mulheres saudáveis e a sua relação com as concentrações dos hormônios estrógeno e progesterona na saliva. Foram avaliadas 39 mulheres com idade entre 19 e 47 anos, com ciclos menstruais regulares e sem morbidades associadas à dor. Todas as mulheres foram orientadas quanto aos propósitos desta pesquisa, e somente participaram do estudo aquelas que preencheram os critérios de inclusão e assinaram o termo de consentimento livre e esclarecido. A avaliação foi realizada em três momentos do ciclo menstrual: fase menstrual, fase folicular e fase lútea. Em cada uma dessas fases foram utilizados os seguintes métodos: coleta da saliva no início de cada sessão, para avaliação dos níveis hormonais; avaliação de fluxo salivar; avaliação sensitiva superficial (dor, tato - IITC Woodland Hills, EUA; frio, calor - MSA II e vibratórios - Somedic, Suécia) aplicada na região do ramo maxilar do nervo trigêmeo e na região do antebraço, ambas no lado direito da paciente; e avaliação das sensibilidades gustativa (doce - glicose, salgado - cloreto de sódio, azedo - ácido cítrico e amargo - ureia) e olfativa (isopropanol em diferentes concentrações). Foram observadas oscilações sensitivas em todas as modalidades de acordo com o momento do ciclo menstrual das mulheres avaliadas, sendo que níveis baixos de estrógeno se associaram a altos limiares de dor de profundidade no braço (p=0,008) e na face (p=0,041), altos limiares táteis (p=0,001) e álgicos superficiais (p=0,006) na face. Em contrapartida, altos níveis de progesterona se associaram a altos limiares de dor de profundidade na face (p=0,033) e altos limiares do sabor salgado (p < 0,001). Concluímos que o estrógeno e a progesterona estão envolvidos na neuromodulação da sensibilidade somestésica, gustativa e olfativa de mulheres, durante o ciclo menstrual / There is a sexual difference on pain perception that is supported by the scientific literature. Moreover, sexual hormones seem to be involved in the modulation of sensory detection and there is evidence of sensory variation during the menstrual cycle. Thus, the aim of this study was to investigate the somatosensory (thermal, painful, tactile, vibratory and electric), gustatory (salty, bitter, sweet, sour) and olfactory thresholds during the menstrual cycle in healthy women and verify association with saliva concentration of estradiol and progesterone. We evaluated 39 women aged between 19 and 47 years, with regular menstrual cycles and with no comorbidities related to pain.All women were instructed about the purposes of the study and only those that signed the informed consent were included. The evaluation wasperformed in three moments of the cycle: menstrual phase, follicular phase and luteal phase. In each of these stages, the following methods were used: saliva collection at the beginning of each session, to assess hormone levels; salivary flow measurement; somatosensory evaluation with quantitative sensory testing (pain, tactile - IITC Woodland Hills, USA; cold and warm - MSA II; and vibration - Somedic, Sweden) applied to the right maxillary branch region of the trigeminal nerve and right forearm region; and gustative (sweet - glucose, salt - sodium chloride, sour - citric acid and bitter - urea) and olfactory (isopropanol at different concentrations) thresholds. All sensory thresholds showed fluctuation during the menstrual cycle. Lower estrogen levels were correlated tohigher deep pain thresholds at the forearm (p=0.008) and face (p=0.041); they were also associated with higher tactile thresholds (p=0.001) and higher superficial pain (p=0.006) thresholds at face.High levels of progesterone were associated with high deep pain threshold at the face and high salty threshold (p < 0.001). In conclusion, estrogen and progesterone seems to be involved in sensory neuromodulation in women, during the menstrual cycle

L’amertume fait partie intégrante de notre alimentation. Elle est par exemple fortement représentée dans certaines boissons (ex: café) ou dans certains légumes tels les crucifères. Néanmoins, la perception de l’amertume varie entre les individus et certains aliments considérés comme bénéfiques pour la santé peuvent être rejetés en raison de leur goût amer. Des facteurs génétiques (ex : polymorphisme génétique des récepteurs du goût amer) ou environnementaux (ex : âge, prise de médicaments) expliquent en partie les variations interindividuelles dans la perception de l’amertume. Cependant, d’autres facteurs péri-récepteurs pourraient intervenir, notamment la composition salivaire. Afin d’investiguer dans un premier temps le lien existant entre le protéome salivaire propre à un individu et sa sensibilité à l’amertume, le seuil de détection du goût amer de la caféine a été mesuré sur 29 hommes sains. Leur salive au repos a été étudiée par électrophorèse mono- et bidimensionnelle. L’analyse par électrophorèse bidimensionnelle de la salive au repos des 6 sujets les plus sensibles et 6 les sujets les moins sensibles à la caféine a permis la détection de 255 spots, dont 26 étaient significativement différents entre hyper- et hyposensibles. L’identification de ces 26 spots a révélé la surexpression de fragments d’alpha amylase, de fragments d’albumine sérique, et de sous-unités alpha de l’immunoglobuline A ainsi que la sous-expression de cystatine SN chez les hypersensibles. Ce dernier résultat a été confirmé par Western Blot. Ceci a permis de formuler une hypothèse sur le rôle de la protéolyse en bouche sur la sensibilité à l’amertume. Dans un deuxième temps et afin d’étudier l’effet des molécules amères sur la composition salivaire, une étude in vitro a été menée sur la lignée cellulaire de glandes salivaires humaines HSG différenciées en acini ou non. Après une mise au point des conditions de différenciation (culture dite en 3D), la cystatine SN a été détectée dans les cellules HSG par Western blot après traitement des cellules à la caféine, à la quinine, et à l’urée. Après traitement à la caféine à 5, 50 ou 100µM, une quantification par ELISA a mis en évidence que la cystatine SN était toujours plus abondante dans les cellules HSG différenciées que dans les cellules non-différenciées. Spécifiquement dans les cellules différenciées, l’exposition à la caféine induisait une sur-expression de cystatine SN, la teneur maximale en cystatine SN étant observée avec la caféine à 50 µM. La présence de cystatine SN a également été détectée dans les milieux de culture / Bitterness is present in every day beverages (e.g. coffee) and foods (e.g. vegetables such as cruciferous plants). However, bitterness is perceived differently among individuals and some foods considered as healthy may be rejected due to their bitter taste. Several genetic (eg. genetic polymorphism of bitter taste receptors) or environmental (eg. age, medications) factors partly explain the interindividual variability in bitterness perception. However, other peri-receptor factors may intervene, in particular salivary composition. First, in order to investigate the link between salivary proteome and sensitivity to bitterness, the detection threshold to the bitter taste of caffeine was measured in 29 male healthy subjects. Their resting saliva was studied by one- and two-dimensional electrophoresis. Two-dimensional electrophoresis revealed that 26 out of 255 spots were significantly different between the 6 hypersensitive and 6 hyposensitive subjects to the bitter taste of caffeine. Identification of the 26 spots revealed an overexpression of amylase-, serum albumin-, and immunoglobulin A fragments, and an underexpression of cystatin SN in hypersensitive subjects. The latter finding was confirmed by Western blotting. These results have led to formulate an hypothesis on the role of in-mouth proteolysis in bitterness perception. Second, in order to study the effect of bitter molecules on salivary composition, an in vitro study was performed on undifferentiated and differentiated human salivary cell line HSG. After setting the experimental conditions for HSG cell differentiation (culture in 3D conditions), cystatin SN was detected in HSG cells by Western blot after treatment with caffeine, quinine, and urea. After cell exposure with caffeine at 5, 50 and 100 µM, quantification by ELISA demonstrated that cystatin SN was always more abundant in differentiated vs undifferentiated HSG cells. Specifically in differentiated cells, caffeine exposure resulted in over-expression of cystatin SN, 50µM inducing the highest effect. Cystatin SN was also detected in culture media of the HSG cells

This study aimed to identify factors associated with taste acuity in healthy older European adults aged 55-87 years, employing a factorial independent design to recruit older adults from centres in France, Italy and United Kingdom. Adults aged 70-87 years (N=387) were recruited in Rome (Italy) (n=108) and Grenoble (France) (n=91) and aged 55-70 years in Northern Ireland (United Kingdom) (n=93) and Clermont-Ferrand (C-F) (France) (n=95). A signal detection theory (SDT) approach was used for detection threshold assessment of the four basic tastes (salt; sweet; bitter; and, sour). Trial data were converted to R-indices. Diet was assessed by means of four day food diaries. Dietary data were converted using WISP and then reduced, using a principal components analysis, to four components: Component 1 'high fat and salt'; Component 2 'high vitamins and fibre'; Component 3 'high fat and carbohydrate'; and, Component 4 'high trace elements'. Socio-demographic information was collected by self report survey. Four separate regression analyses were carried out, one for each of the four basic taste qualities (sweet; sour; bitter; salt). Mean ROC scores for each taste quality were the response variables and age, sex, country, social class and dietary components were predictor variables. The main predictors of taste acuity were age, sex, social class and country, which had differential effects for each taste quality. These data suggest that socio-demographic and cultural factors should be taken into account when considering taste acuity in older people.

Dans ce travail, nous démontrons que STIM1, un senseur calcique activé par la déplétion du Ca2+ intracellulaire du réticulum endoplasmique, est indispensable pour la signalisation calcique et la préférence oro-sensorielle du gras. Nous observons que l'acide linoléique (LA), en activant les phospholipases A2 via CD36, produit de l’acide arachidonique (AA) et de la lyso-phosphatidylcholine (lyso-PC). Cette activation déclenche un influx calcique dans les cellules CD36-positives, et induit la production du facteur CIF (Ca2+ Influx Factor). CIF, AA et lyso-PC exercent différentes actions sur l'ouverture des canaux SOC (Stored Operated Calcium Channel) constitués de protéines Orai et contrôlés par STIM1. Par ailleurs, les souris au phénotype Stim1-/- perdent la préférence spontanée pour les lipides et la libération de la sérotonine à partir des cellules gustatives dans le milieu extracellulaire chez les animaux sauvages. Nous demontrons aussi que la signalisation calcique médiée via CD36 est doublement modulée lors de l’obésité. L’augmentation de la [Ca2+]i dans les cellules gustatives observée chez le Psammomys obesus, un modèle d’obésité nutritionelle, est fortement diminuée chez les souris rendues obèses par un regime hyperlipidique. Nous avons constaté également que l’interaction de LA avec le CD36 induit l’activation des MAP Kinases de la voie MEK1/2/ERK1/2/Elk-1 qui est non seulement à l’origine de l’activation des aires cérébrales telles que le NTS, le noyau arqué, l’hippocampe mais aussi indispensable pour la préférence spontanée pour les lipides alimentaires. Nos résultats suggèrent pour la prémière fois, que la voie ERK1/2 des MAPK et la signalisation calcique lipidique controlée par STIM1 sont impliquées dans la perception oro-gustative des lipides / In this work, we demonstrate that stromal interaction molecule 1 (STIM1), a sensor of Ca2+ depletion in the endoplasmic reticulum, mediates fatty acid–induced Ca2+ signaling in the mouse tongue and fat preference. We showed that linoleic acid (LA) induced the production of arachidonic acid (AA) and lysophosphatidylcholine (Lyso-PC) by activating multiple phospholipase A2 isoforms via CD36. This activation triggered Ca2+ influx in lingual CD36-positive taste bud cells (TBCs) purified from mouse CVP. LA also induced the production of Ca2+ influx factor (CIF). STIM1 was found to regulate LA-induced CIF production and the opening of store-operated Ca2+ (SOC) channels. Furthermore, CD36-positive TBCs from Stim1–/– mice failed to release serotonin, and Stim1–/– mice lost the spontaneous preference for fat that was observed in wild-type animals. We also demonstrate that the calcium-mediated signaling via CD36 is doubly modulated in obesity. The increase in [Ca2+]i in taste bud cells observed in Psammomys obesus, a model of nutritional obesity is strongly reduced in diet-induced obese (DIO) mice. We also found that the interaction of LA with CD36 induces activation of MAP Kinases MEK1/2/ERK1/2/Elk-1 pathway that is not only responsible for the activation of NTS, arcuate nucleus, and the hippocampus in the brain but also essential for the spontaneous preference for fat food. Our results suggest for the first time, that ERK1/2 MAPK pathway and lipid-induced calcium signaling controlled by STIM1 are involved in oro-gustatory perception of dietary lipids

INTRODUÇÃO: A obesidade infantil é um importante problema de saúde pública e apresenta impacto direto na qualidade de vida das crianças e adolescentes, bem como no desenvolvimento futuro de doenças crônicas. O padrão alimentar rico em gordura e açúcar, e com baixo aporte de fibra dietética, vitaminas e minerais é reconhecido como fator de risco para o surgimento da obesidade, no entanto os fatores que contribuem para a preferência por alimentos ricos nestes nutrientes não são bem estabelecidos. O sabor dos alimentos é reconhecido como um importante preditor das escolhas alimentares, e os polimorfismos nos genes que codificam os receptores do sabor podem explicar a variabilidade da preferência e consumo alimentar na população. OBJETIVO: Avaliar a influência de polimorfismos de genes de receptores de sabor gorduroso (CD36), doce (TAS1R2) e amargo (TAS2R38) no consumo alimentar e no perfil metabólico de crianças e adolescentes obesos. MÉTODOS: Estudo transversal com 668 crianças e adolescentes obesos e um grupo controle de 135 crianças eutróficas, de ambos os gêneros. Foi realizado o estudo molecular dos polimorfismos de nucleotídeo único (SNPs) rs1761667 e rs1527483 do CD36, rs9701796 e rs35874116 do TAS1R2, e rs1726866 e rs713598 do TAS2R38, bem como análise do consumo alimentar e perfil metabólico. RESULTADOS: Em relação ao CD36, o alelo A do rs1761667 relacionou-se com menor consumo de lipídios totais, gorduras poli e monoinsaturadas, consumo de alimentos de sabor gorduroso, ingestão de óleos vegetais e açúcares totais em obesos. O alelo A do rs1527483 associou-se com menor percentil de pressão arterial diastólica, menor massa gorda e maior massa livre de gordura em obesos. Quanto ao gene TAS1R2, a variante rs9701796 teve maior risco metabólico segundo a razão circunferência da cintura-estatura (RCE), bem como relação com maior consumo de achocolatado em pó em obesos. Já a variante rs35874116 mostrou relação com a menor ingestão de fibras dietéticas em obesos. No TAS2R38, o alelo G do rs1726866 foi associado com menor consumo de gorduras monoinsaturadas e maior consumo de açúcares totais, em obesos. O alelo G do rs713598 mostrou relação com maior consumo de carboidratos, consumo de alimentos de sabor doce, refrigerantes e menor ingestão de fibras pelos indivíduos eutróficos. CONCLUSÃO: Não houve relação entre genótipos e risco de obesidade. Os achados mostram a associação entre polimorfismos dos genes de receptores de sabor com o consumo alimentar, indicando diferenças entre obesos e magros, e alelos de proteção e de risco cardiometabólico, respectivamente dos genes CD36 e TAS1R2 / BACKGROUND: Childhood obesity is a major public health problem and it has a direct impact on the quality of life of children and adolescents, as well as the future risk for development of chronic diseases. The dietary pattern rich in fats and sugars associated to the low intake of dietary fibers, vitamins and minerals is widespread for the rise of obesity. However the factors that contribute to the preference for foods rich in these nutrients are not well established. Taste is recognized as an important predictor of food choices, and polymorphisms in genes encoding its receptors may explain the variability of taste preference and food intake on population. OBJECTIVE: To evaluate the influence of polymorphisms of fat (CD36), sweet (TAS1R2) and bitter (TAS2R38) taste receptor genes in diet and metabolic profile in obese children and adolescents. METHODS: Cross-sectional study with 668 obese children and adolescents and a control group of 135 normal-weight children. The molecular study was made for single nucleotide polymorphisms (SNPs) rs1761667 and rs1527483 of CD36, rs9701796 and rs35874116 of TAS1R2, rs1726866 and rs713598 of TAS2R38, and the analysis of food intake and metabolic profile. RESULTS: In relation to CD36, the A allele of rs1761667 was associated with lower intake of total fat, poly and monounsaturated fats, consumption of fatty flavor food, intake of vegetable oils and total sugars in obese. The A allele of rs1527483 was associated with lower percentile of diastolic blood pressure, lower fat mass and increased fat-free mass in obese. Regarding TAS1R2 gene, the variant rs9701796 was associated to increased metabolic risk according to waist-height ratio, as well as with higher consumption of chocolate powder in obese. The variant rs35874116 showed a lower intake of dietary fiber. In TAS2R38, the G allele of rs1726866 was associated with a lower intake of monounsaturated fat and a higher intake of total sugars in obese. The G allele of rs713598 was related to the higher carbohydrate intake, consumption of sweet tasting food, soda drinks and less fiber intake by normal weight children. CONCLUSION: There was no relationship between genotypes and risk of obesity. The findings show the association between polymorphisms of taste receptor genes with dietary intake, indicating differences between obese and lean children, as well as the protective and risk alleles for cardiometabolic risk in CD36 and TAS1R2, respectively

INTRODUÇÃO: A obesidade infantil é um importante problema de saúde pública e apresenta impacto direto na qualidade de vida das crianças e adolescentes, bem como no desenvolvimento futuro de doenças crônicas. O padrão alimentar rico em gordura e açúcar, e com baixo aporte de fibra dietética, vitaminas e minerais é reconhecido como fator de risco para o surgimento da obesidade, no entanto os fatores que contribuem para a preferência por alimentos ricos nestes nutrientes não são bem estabelecidos. O sabor dos alimentos é reconhecido como um importante preditor das escolhas alimentares, e os polimorfismos nos genes que codificam os receptores do sabor podem explicar a variabilidade da preferência e consumo alimentar na população. OBJETIVO: Avaliar a influência de polimorfismos de genes de receptores de sabor gorduroso (CD36), doce (TAS1R2) e amargo (TAS2R38) no consumo alimentar e no perfil metabólico de crianças e adolescentes obesos. MÉTODOS: Estudo transversal com 668 crianças e adolescentes obesos e um grupo controle de 135 crianças eutróficas, de ambos os gêneros. Foi realizado o estudo molecular dos polimorfismos de nucleotídeo único (SNPs) rs1761667 e rs1527483 do CD36, rs9701796 e rs35874116 do TAS1R2, e rs1726866 e rs713598 do TAS2R38, bem como análise do consumo alimentar e perfil metabólico. RESULTADOS: Em relação ao CD36, o alelo A do rs1761667 relacionou-se com menor consumo de lipídios totais, gorduras poli e monoinsaturadas, consumo de alimentos de sabor gorduroso, ingestão de óleos vegetais e açúcares totais em obesos. O alelo A do rs1527483 associou-se com menor percentil de pressão arterial diastólica, menor massa gorda e maior massa livre de gordura em obesos. Quanto ao gene TAS1R2, a variante rs9701796 teve maior risco metabólico segundo a razão circunferência da cintura-estatura (RCE), bem como relação com maior consumo de achocolatado em pó em obesos. Já a variante rs35874116 mostrou relação com a menor ingestão de fibras dietéticas em obesos. No TAS2R38, o alelo G do rs1726866 foi associado com menor consumo de gorduras monoinsaturadas e maior consumo de açúcares totais, em obesos. O alelo G do rs713598 mostrou relação com maior consumo de carboidratos, consumo de alimentos de sabor doce, refrigerantes e menor ingestão de fibras pelos indivíduos eutróficos. CONCLUSÃO: Não houve relação entre genótipos e risco de obesidade. Os achados mostram a associação entre polimorfismos dos genes de receptores de sabor com o consumo alimentar, indicando diferenças entre obesos e magros, e alelos de proteção e de risco cardiometabólico, respectivamente dos genes CD36 e TAS1R2 / BACKGROUND: Childhood obesity is a major public health problem and it has a direct impact on the quality of life of children and adolescents, as well as the future risk for development of chronic diseases. The dietary pattern rich in fats and sugars associated to the low intake of dietary fibers, vitamins and minerals is widespread for the rise of obesity. However the factors that contribute to the preference for foods rich in these nutrients are not well established. Taste is recognized as an important predictor of food choices, and polymorphisms in genes encoding its receptors may explain the variability of taste preference and food intake on population. OBJECTIVE: To evaluate the influence of polymorphisms of fat (CD36), sweet (TAS1R2) and bitter (TAS2R38) taste receptor genes in diet and metabolic profile in obese children and adolescents. METHODS: Cross-sectional study with 668 obese children and adolescents and a control group of 135 normal-weight children. The molecular study was made for single nucleotide polymorphisms (SNPs) rs1761667 and rs1527483 of CD36, rs9701796 and rs35874116 of TAS1R2, rs1726866 and rs713598 of TAS2R38, and the analysis of food intake and metabolic profile. RESULTS: In relation to CD36, the A allele of rs1761667 was associated with lower intake of total fat, poly and monounsaturated fats, consumption of fatty flavor food, intake of vegetable oils and total sugars in obese. The A allele of rs1527483 was associated with lower percentile of diastolic blood pressure, lower fat mass and increased fat-free mass in obese. Regarding TAS1R2 gene, the variant rs9701796 was associated to increased metabolic risk according to waist-height ratio, as well as with higher consumption of chocolate powder in obese. The variant rs35874116 showed a lower intake of dietary fiber. In TAS2R38, the G allele of rs1726866 was associated with a lower intake of monounsaturated fat and a higher intake of total sugars in obese. The G allele of rs713598 was related to the higher carbohydrate intake, consumption of sweet tasting food, soda drinks and less fiber intake by normal weight children. CONCLUSION: There was no relationship between genotypes and risk of obesity. The findings show the association between polymorphisms of taste receptor genes with dietary intake, indicating differences between obese and lean children, as well as the protective and risk alleles for cardiometabolic risk in CD36 and TAS1R2, respectively