Brain-derived neurotrophic factor overexpression in taste buds diminishes chemotherapy induced taste loss.

Vismodegib is used in patients suffering from advanced basal cell carcinoma (BCC), but 100% of the patients taking it report dysgeusia and 50% discontinue the treatment. Treatment with neurotrophic factors can stimulate neuronal survival and functional improvement in injured organs. Here, we analysed novel transgenic mouse lines in which brain-derived neurotrophic factor (BDNF) is overexpressed in taste buds, to examine whether higher levels of BDNF would reduce or prevent negative side effects of vismodegib in the taste system. BDNF plays crucial roles for development, target innervation, and survival of gustatory neurons and taste buds. The behavioural test in this study showed that vehicle-treated wild-type mice prefered 10 mM sucrose over water, whereas vismodegib treatment in wild-type mice caused total taste loss. Gustducin-BDNF mice had a significantly increased preference for low concentration of sucrose solution over water compared to wild-type mice, and most importantly the transgenic mice were able to detect low concentrations of sucrose following vismodegib treatment. We evaluated taste cell morphology, identity, innervation and proliferation using immunohistochemistry. All drug-treated mice exhibited deficits, but because of a possible functional upcycled priming of the peripheral gustatory system, GB mice demonstrated better morphological preservation of the peripheral gustatory system. Our study indicates that overexpression of BDNF in taste buds plays a role in preventing degeneration of taste buds. Counteracting the negative side effects of vismodegib treatment might improve compliance and achieve better outcome in patients suffering from advanced BCC.

A Mechanistic Overview of Taste Bud Maintenance and Impairment in Cancer Therapies.

Since the early 20th century, progress in cancer therapies has significantly improved disease prognosis. Nonetheless, cancer treatments are often associated with side effects that can negatively affect patient well-being and disrupt the course of treatment. Among the main side effects, taste impairment is associated with depression, malnutrition, and morbid weight loss. Although relatively common, taste disruption associated with cancer therapies remains poorly understood. Here, we review the current knowledge related to the molecular mechanisms underlying taste maintenance and disruption in the context of cancer therapies.

The taste of neuroinflammation: Molecular mechanisms linking taste sensing to neuroinflammatory responses.

Evidence indicates a critical role of neuroinflammatory response as an underlying pathophysiological process in several central nervous system disorders, including neurodegenerative diseases. However, the molecular mechanisms that trigger neuroinflammatory processes are not fully known. The discovery of bitter taste receptors in regions other than the oral cavity substantially increased research interests on their functional roles in extra-oral tissues. It is now widely accepted that bitter taste receptors, for instance, in the respiratory, intestinal, reproductive and urinary tracts, are crucial not only for sensing poisonous substances, but also, act as immune sentinels, mobilizing defense mechanisms against pathogenic aggression. The relatively recent discovery of bitter taste receptors in the brain has intensified research investigation on the functional implication of cerebral bitter taste receptor expression. Very recent data suggest that responses of bitter taste receptors to neurotoxins and microbial molecules, under normal condition, are necessary to prevent neuroinflammatory reactions. Furthermore, emerging data have revealed that downregulation of key components of the taste receptor signaling cascade leads to increased oxidative stress and inflammasome signaling in neurons that ultimately culminate in neuroinflammation. Nevertheless, the mechanisms that link taste receptor mediated surveillance of the extracellular milieu to neuroinflammatory responses are not completely understood. This review integrates new data on the molecular mechanisms that link bitter taste receptor sensing to neuroinflammatory responses. The role of bitter taste receptor-mediated sensing of toxigenic substances in brain disorders is also discussed. The therapeutic significance of targeting these receptors for potential treatment of neurodegenerative diseases is also highlighted.

Identification of an oral microbiota signature associated with an impaired orosensory perception of lipids in insulin-resistant patients.

AIMS: Type 2 diabetes leads to multiple sensory dysfunctions affecting notably the gustatory sensitivity. Although this sensory defect, by impacting food choices, might lead to unhealthy eating behavior, underlying mechanisms remains poorly studied. We have recently reported that the composition of microbiota in contact with circumvallate gustatory papillae might affect the orosensory perception of lipids in lean and normoglycemic obese subjects. This finding has prompted us to explore whether such a phenomenon also occurs in diabetic obese patients. METHODS: The composition of microbiota surrounding the circumvallate papillae was analyzed in combination with the linoleic acid perception thresholds in male insulin-resistant patients and weight-matched healthy controls. Two complementary comparisons were performed: (1) controls vs diabetic and (2) diabetic low-lipid tasters versus diabetic high-lipid tasters. RESULTS: Despite subtle modifications in the oral microbiota composition, comparison of orosensory lipid perception in controls and diabetic subjects did not lead to discriminating data due to the large inter-individual variability of linoleic acid perception thresholds. In contrast, specific bacterial signatures were found by comparing diabetic low- and high-lipid tasters leading to differential molecular pathways. Surprisingly, a lower fatty taste perception was mainly found in patients treated with metformin and/or statins, suggesting a possible side effect of these antidiabetic and/or hypolipidemic drugs on taste acuity. CONCLUSIONS: Collectively, these data show that the diabetic patients with defective fatty taste detection are characterized by a specific microbiota metabolism at the circumvallate papillae levels, this occurrence seeming amplified by drugs commonly used to counteract the damaging metabolic effects of T2D. Trial registration for original previous studies: ClinicalTrials.gov #NCT02028975.

The prospective role of mesenchymal stem cells exosomes on circumvallate taste buds in induced Alzheimer's disease of ovariectomized albino rats: (Light and transmission electron microscopic study).

OBJECTIVE: To elucidate the effect of Alzheimer's disease on the structure of circumvallate papilla taste buds and the possible role of exosomes on the taste buds in Alzheimer's disease. DESIGN: Forty two ovariectomized female adult albino rats were utilized and divided into: Group I: received vehicle. Group II: received aluminum chloride to induce Alzheimer's disease. Group III: after the induction of Alzheimer's disease, each rat received single dose of exosomes then left for 4 weeks. The circumvallate papillae were prepared for examination by light and transmission electron microscope. STATISTICAL ANALYSIS: histomorphometric data were statistically analyzed. RESULTS: Histological examination of circumvallate papilla in Group I showed normal histological features. Group II revealed distorted features. Group III illustrated nearly normal histological features of circumvallate. Silver impregnation results showed apparently great number of heavily impregnated glossopharyngeal nerve fibers in both Groups I & III but markedly decreased in Group II. Synaptophysin-immunoreactivity was strong in Group I, mild in Group II and moderate in Group III. The ultra-structural examination of taste bud cells revealed normal features in Group I, distorted features in Group II and almost normal features in Group III. Statistically highest mean of Synaptophysin-immunoreactivity area% was for Group I, followed by Group III, and the least value was for Group II. CONCLUSIONS: Alzheimer's disease has degenerative effects. Bone marrow mesenchymal stem cell (BM-MSC)-derived exosomes have the ability to improve the destructive changes induced by Alzheimer's disease.

T1R2+T1R3-independent chemosensory inputs contributing to behavioral discrimination of sugars in mice.

Simple sugars are thought to elicit a unitary sensation, principally via the "sweet" taste receptor type 1 taste receptor (T1R)2+T1R3, yet we previously found that rats with experience consuming two metabolically distinct sugars, glucose and fructose, subsequently licked more for glucose than fructose, even when postingestive influences were abated. The results pointed to the existence of an orosensory receptor that binds one sugar but not the other and whose signal is channeled into neural circuits that motivate ingestion. Here we sought to determine the chemosensory nature of this signal. First, we assessed whether T1R2 and/or T1R3 are necessary to acquire this behavioral discrimination, replicating our rat study in T1R2+T1R3 double-knockout (KO) mice and their wild-type counterparts as well as in two common mouse strains that vary in their sensitivity to sweeteners [C57BL/6 (B6) and 129X1/SvJ (129)]. These studies showed that extensive exposure to multiple concentrations of glucose and fructose in daily one-bottle 30-min sessions enhanced lick responses for glucose over fructose in brief-access tests. This was true even for KO mice that lacked the canonical "sweet" taste receptor. Surgical disconnection of olfactory inputs to the forebrain (bulbotomy) in B6 mice severely disrupted the ability to express this experience-dependent sugar discrimination. Importantly, these bulbotomized B6 mice exhibited severely blunted responsiveness to both sugars relative to water in brief-access lick tests, despite the fact that they have intact T1R2+T1R3 receptors. The results highlight the importance of other sources of chemosensory and postingestive inputs in shaping and maintaining "hardwired" responses to sugar.

Unilateral nasal obstruction alters sweet taste preference and sweet taste receptors in rat circumvallate papillae.

Nasal obstruction causes mouth breathing, and affects the growth and development of craniofacial structures, muscle function in the stomatognathic system, and the taste perceptive system. However, the detailed mechanism underlying the effects of nasal obstruction on taste perception has not been fully elucidated. In this study, we investigated this mechanism using the two-bottle taste preference test, immunohistological analysis, and quantification of the mRNA expression of taste-related molecules in the circumvallate papillae. Neonatal male Wistar rats were divided randomly into control and experimental groups. Rats in the experimental group underwent unilateral nasal obstruction by cauterization of the external nostril at the age of 8 days. Arterial oxygen saturation (SpO2) was recorded in awake rats using collar clip sensors. Taste preference for five basic taste solutions was evaluated. Immunohistochemical analysis and quantitative real-time polymerase chain reaction (RT-PCR) were conducted to evaluate the expressions of taste-related molecules in the taste cells of the circumvallate papillae. Body weights were similar between the two groups throughout the experimental period. The SpO2 in the 7- to 12-week-old rats in the experimental group was significantly lower than that in the age-matched rats in the control group. In the two-bottle taste preference test, the sensitivities to sweet taste decreased in the experimental group. The mRNA expression of T1R2, T1R3, α-gustducin, and PLCß2 was significantly lower in the experimental group than in the control group as determined by quantitative RT-PCR, and the immunohistochemical staining for α-gustducin and PLCß2 was less prominent. These findings suggest that nasal obstruction may affect sweet taste perception via the reduced expression of taste-related molecules in the taste cells in rat circumvallate papillae.

Gustatory dysfunction in relation to circumvallate papilla's taste buds structure upon unilateral maxillary molar extraction in Wistar rats: an in vivo study.

Background: The interaction between taste sensation and dentoalveolar innervation is still under research.  teeth loss can alter taste thresholds in humans, but the underlying mechanisms are still obscure. This study investigated the effect of unilateral maxillary molars extraction on the structure of circumvallate papilla in rats. Methods: Thirty-two male Wister rats, aged 3-4 months were randomly distributed into four groups (one control and 3 experimental ) each including 8 animals. The rats were euthanized 3, 6 or 9 weeks following the procedure. The changes in trough length and the taste buds structure and number of both sides of CVP were investigated using routine histological examination followed by statistical analysis. Results: the trough toward the extraction side was obviously shorter with a noticeable decrease of taste buds' number than the non-extraction side. Taste buds were reduced in size and most of them showed signs of degeneration which was more evident in group II followed by group III, less deformity detected in group IV in comparison to the preceding 2 experimental groups. the non-extraction side of all experimental groups showed normal trough length and generally normal histology of taste buds.   Conclusions: Maxillary molars extraction has a degenerative effect on the structure of  taste buds and gustatory epithelium which were more marked at the extraction side and showed improvement upon elongation of follow up period.

A longitudinal study of altered taste and smell perception and change in blood pressure.

BACKGROUND AND AIMS: Previous studies suggest that olfactory receptors, which mediate smell chemosensation, are located in the kidney and involved in blood pressure regulation. Mammalian epithelial sodium channels located in taste receptor cells are also found to participate in blood pressure regulation. However, there is currently no human study that has examined the association between taste and smell function and blood pressure. We thus conducted a longitudinal study to examine whether participants with altered taste and smell perception had larger increases in blood pressure compared with those without altered perception in a community-based cohort. METHODS AND RESULTS: The study included 5190 Chinese adults (4058 men and 1132 women) who were normotensive at baseline. Taste and smell perception were assessed via questionnaire in 2012 (baseline). Blood pressure was measured in 2012 and 2014 to determine relative change in blood pressure. Mean differences of 2-year blood pressure change and 95% confidence intervals (CIs) across four categories of taste and smell perception were calculated after adjusting for known risk factors for hypertension. After adjusting for potential confounders, individuals with altered taste and smell perception had larger increases in systolic blood pressure (adjusted mean difference = 5.1 mmHg, 95% CI: 0.1-10.0, p-value: 0.04) and mean arterial pressure (adjusted mean difference = 3.8 mmHg, 95% CI: 0.4-7.1, p-value: 0.03) after two years of follow-up compared with those having neither altered taste nor altered smell perception. No significant association was observed in individuals with altered taste or smell perception only. CONCLUSION: Our results suggest an association between chemosensory function and blood pressure.

Taste alterations and cancer treatment.

PURPOSE OF REVIEW: In this review, we explore issues on the physiology of taste and smell and we critically review recent literature of taste and smell changes and the impact on food preferences throughout the cancer treatment trajectory. RECENT FINDINGS: Subjective measurements such as validated questionnaires can be valuable for the clinical setting and many studies describe taste and smell changes by self-report. Because both smell and taste are interrelated, these subjective results are difficult to interpret. Recent studies have looked more specifically at one type of malignancy with a consistent and homogeneous treatment with chemotherapy using objective taste assessment such as electrogustometry, liquid tastants or filter paper strips. SUMMARY: Taste is a combination of different sensations: smell, texture, temperature and saliva play an important role in determining the overall flavor of food. The mechanism for taste and smell abnormalities in cancer patients treated with systemic therapies remains unclear.

Gustatory Function in Patients With Chronic Rhinosinusitis.

OBJECTIVES: Recent research has shown that taste receptors in airway epithelial cells are involved in defending against upper respiratory tract infection. The aim of the present study was to investigate gustatory function in patients with chronic rhinosinusitis (CRS). METHODS: Taste function was assessed using the extended "taste strip" test in 37 patients with CRS (20 males, 17 females; mean age = 32.1 years; range, 20-82 years) and 135 healthy controls (70 males, 65 females; mean age = 29.5 years; range, 18-84 years). RESULTS: The mean (±SD) total extended taste score was 12.8 (±3.5) in patients and 14.5 (±3.2) in controls. Analysis of variance indicated an interaction of sinusitis and gender ( P < .05) with significantly lower total scores and significantly poorer results for the bitter taste among male patients compared to controls ( P < .01). In addition, CRS patients exhibited a trend toward decreased sweet taste perception compared to controls, but this did not reach significance ( P = .051). CONCLUSIONS: Patients with CRS exhibited decreased gustatory function compared to healthy controls. The effect was most pronounced for bitter taste. Thus, the assessment of gustatory function seems to be useful for detecting potential risk factors for recurrent upper respiratory tract infection.

A case-control evaluation of fungiform papillae density in burning mouth syndrome.

HYPOTHESIS: It has been hypothesized that high fungiform papillae density may be a risk factor for developing the taste and pain alterations characteristic of burning mouth syndrome. OBJECTIVE: Evaluate whether fungiform papillae density, taste sensitivity, and mechanical pain sensitivity differ between burning mouth syndrome cases and controls. STUDY DESIGN: This case-control study compared cases diagnosed with primary burning mouth syndrome with pain-free controls. METHODS: Participants (17 female cases and 23 female controls) rated the intensity of sucrose, sodium chloride, citric acid, and quinine applied separately to each side of the anterior tongue and sampled whole mouth. Mechanical pain sensitivity was assessed separately for each side of the tongue using weighted pins. Digital photographs of participants' tongues were used to count fungiform papillae. RESULTS: Burning mouth syndrome cases had increased whole mouth taste intensity. Cases also had increased sensitivity to quinine on the anterior tongue, as well as increased mechanical pain sensitivity on the anterior tongue. Fungiform papillae density did not differ significantly between cases and controls. Fungiform papillae density on the left and right sides of the tongue were correlated in controls; however, there was no left/right side correlation in cases. CONCLUSION: Cases had increased pain and taste perception on the anterior tongue. The lack of correlation between left and right fungiform papillae density in cases may be an indication of asymmetrical lingual innervation in these patients. LEVEL OF EVIDENCE: 3b. Laryngoscope, 128:841-846, 2018.

Recovery of taste organs and sensory function after severe loss from Hedgehog/Smoothened inhibition with cancer drug sonidegib.

Striking taste disturbances are reported in cancer patients treated with Hedgehog (HH)-pathway inhibitor drugs, including sonidegib (LDE225), which block the HH pathway effector Smoothened (SMO). We tested the potential for molecular, cellular, and functional recovery in mice from the severe disruption of taste-organ biology and taste sensation that follows HH/SMO signaling inhibition. Sonidegib treatment led to rapid loss of taste buds (TB) in both fungiform and circumvallate papillae, including disruption of TB progenitor-cell proliferation and differentiation. Effects were selective, sparing nontaste papillae. To confirm that taste-organ effects of sonidegib treatment result from HH/SMO signaling inhibition, we studied mice with conditional global or epithelium-specific Smo deletions and observed similar effects. During sonidegib treatment, chorda tympani nerve responses to lingual chemical stimulation were maintained at 10 d but were eliminated after 16 d, associated with nearly complete TB loss. Notably, responses to tactile or cold stimulus modalities were retained. Further, innervation, which was maintained in the papilla core throughout treatment, was not sufficient to sustain TB during HH/SMO inhibition. Importantly, treatment cessation led to rapid and complete restoration of taste responses within 14 d associated with morphologic recovery in about 55% of TB. However, although taste nerve responses were sustained, TB were not restored in all fungiform papillae even with prolonged recovery for several months. This study establishes a physiologic, selective requirement for HH/SMO signaling in taste homeostasis that includes potential for sensory restoration and can explain the temporal recovery after taste dysgeusia in patients treated with HH/SMO inhibitors.

[Taste dysfunction (dysgeusia) and radioiodine therapy of thyroid cancer - be aware of side effects by antidepressants and sedatives. Vorschädigung durch Antidepressiva und Sedativa beachten]. / Geschmacksstörung (Dysgeusie) und Radioiodtherapie des Schilddrüsenkarzinoms. Vorschädigung durch Antidepressiva und Sedativa beachten.

In addition to xerostomia, taste dysfunction (hypo-, dysgeusia) is an independent side effect of radioiodine therapy of thyroid cancer. Hypogeusia results from damage of the small mucous salivary glands in the vicinity of the taste buds. Particularly in those patients, who are treated with drugs such as antidepressants or sedatives, taste dysfunction becomes frequently clinically symptomatic. If feasible, therapy regimens bearing a potential risk for taste dysfunction should be switched. Additional damage to taste function should be minimalized, including cessation of smoking, change of agents for dental hygiene, and change of toothpaste. If the medical indication for ablative radioiodine therapy is based on the patient's decision, the patient should be informed about alternative strategies. Potential clinical consequences of the sialadenitis (xerostomia, alteration in taste, risk of caries and tooth extraction, lacrimal gland dysfunction, tearing and need of dacryocystorhinostomy) should be revealed completely. Adapted to the initial risk of relapse, the 131I-activity for ablation should be reduced to the latest standard of care. Clinical data are currently too heterogeneous to decide whether rhTSH might reduce the rate of dysgeusia. The specialist in nuclear medicine should be aware of the multifactorial causes of taste dysfunction, in particular if the patient seeks medical advice after radioiodine therapy.

Taste function assessed by electrogustometry in burning mouth syndrome: a case-control study.

OBJECTIVE: Idiopathic burning mouth syndrome (iBMS) is characterized by oral persistent pain without any clinical or biological abnormality. The aim of this study was to evaluate taste function in iBMS subjects and healthy controls. MATERIAL AND METHODS: Electrogustometric thresholds (EGMt) were recorded in 21 iBMS patients and 21 paired-matched controls at nine loci of the tongue assessing fungiform and foliate gustatory papillae function. Comparison of EGMt was performed using the nonparametric Wilcoxon signed-rank test. A correlation between EGMt and self-perceived pain intensity assessed using a visual analogic scale (VAS) was analyzed with the Spearman coefficient. The level of significance was fixed at P < 0.05. RESULTS: Mean EGMt were significantly increased with iBMS for right side of the dorsum of the tongue and right lateral side of the tongue (P < 0.05). In the iBMS group, VAS scores were significantly correlated to EGMt at the tip of the tongue (r = -0.59; P < 0.05) and at the right and left lateral sides of the tongue (respectively, r = -0.49 and r = -0.47; P < 0.05). CONCLUSION: These data depicted impaired taste sensitivity in iBMS patients within fungiform and foliate taste bud fields and support potent gustatory/nociceptive interaction in iBMS.

Alteration of taste buds in experimental cirrhosis. Is there correlation with human hypogeusia? / Alteração de paladar em um modelo experimental de cirrose. Existe correlação com hipogeusia humana?

ABSTRACT Background The inherent complications of cirrhosis include protein-calorie malnutrition and micronutrient deficiencies.Changes in taste are detrimental to the nutritional status, and the mechanism to explain these changes is not well documented in the cirrhotic patients. Objective To evaluate the taste buds of cirrhotic rats. Methods Fourteen male Wistar rats were evaluated. After 16 weeks, the liver was removed to histologically diagnose cirrhosis, and blood was collected to perform liver integrity tests. The tongue was removed for histological examination and immunohistochemistry using antibodies against protein gene product PGP 9.5 and the sweet taste receptors T1R2 and T1R3. Morphological changes were determined by scanning electron microscopy. Serum zinc levels were measured. Results The cirrhotic animals, but not the control animals, exhibited zinc deficiency. In both groups, there was positive immunoreactivity for type II and III cells and T1R2 receptors. The cirrhotic animals had no immunoreactivity for T1R3 receptors. Scanning electron microscopy analysis of the cirrhotic group revealed a uniform tapering of the gustatory papillae. Conclusion In conclusion the experimental cirrhosis model mimicked the biochemical and histological parameters of human cirrhosis, therefore enabling a study of the gustatory papillae and taste buds.

RESUMO Contexto As complicações inerentes de cirrose incluem a desnutrição proteico-calórica e deficiências de micronutrientes. Alterações no paladar são prejudiciais para o estado nutricional e o mecanismo para explicar essas mudanças não é bem documentada nos pacientes cirróticos. Objetivo Avaliar as papilas gustativas de ratos cirróticos. Métodos Foram avaliados 14 ratos Wistar machos. Após 16 semanas, o fígado foi removido para diagnosticar histologicamente cirrose, e o sangue foi colhido para efetuar testes de integridade hepática. A língua foi removida para exame histológico e imuno-histoquímica utilizando anticorpos contra o gene da proteína PGP 9.5 e os receptores de sabor doce T1R2 e T1R3. As alterações morfológicas foram determinadas por microscopia eletrônica de varredura e os níveis de zinco no soro foram medidos. Resultados Os animais cirróticos, em relação aos animais controle, apresentaram deficiência de zinco significativa. Em ambos os grupos, houve imunorreatividade positiva para o tipo II e células III e receptores T1R2. Os animais cirróticos não tinham imunoreactividade para receptores T1R3. Microscopia eletrônica de varredura do grupo cirrótico revelou um afilamento uniforme das papilas gustativas. Conclusão O modelo de cirrose experimental imitou os parâmetros bioquímicos e histológicos de cirrose humana, portanto, permitindo um estudo das papilas gustativas e paladar.

ALTERATION OF TASTE BUDS IN EXPERIMENTAL CIRRHOSIS. Is there correlation with human hypogeusia?

BACKGROUND: The inherent complications of cirrhosis include protein-calorie malnutrition and micronutrient deficiencies.Changes in taste are detrimental to the nutritional status, and the mechanism to explain these changes is not well documented in the cirrhotic patients. OBJECTIVE: To evaluate the taste buds of cirrhotic rats. METHODS: Fourteen male Wistar rats were evaluated. After 16 weeks, the liver was removed to histologically diagnose cirrhosis, and blood was collected to perform liver integrity tests. The tongue was removed for histological examination and immunohistochemistry using antibodies against protein gene product PGP 9.5 and the sweet taste receptors T1R2 and T1R3. Morphological changes were determined by scanning electron microscopy. Serum zinc levels were measured. RESULTS: The cirrhotic animals, but not the control animals, exhibited zinc deficiency. In both groups, there was positive immunoreactivity for type II and III cells and T1R2 receptors. The cirrhotic animals had no immunoreactivity for T1R3 receptors. Scanning electron microscopy analysis of the cirrhotic group revealed a uniform tapering of the gustatory papillae. CONCLUSION: In conclusion the experimental cirrhosis model mimicked the biochemical and histological parameters of human cirrhosis, therefore enabling a study of the gustatory papillae and taste buds.

Multiple loss-of-function variants of taste receptors in modern humans.

Despite recent advances in the knowledge of interindividual taste differences, the underlying genetic backgrounds have remained to be fully elucidated. Much of the taste variation among different mammalian species can be explained by pseudogenization of taste receptors. Here I investigated whether the most recent disruptions of taste receptor genes segregate with their intact forms in modern humans by analyzing 14 ethnically diverse populations. The results revealed an unprecedented prevalence of 25 segregating loss-of-function (LoF) taste receptor variants, identifying one of the most pronounced cases of functional population diversity in the human genome. LoF variant frequency in taste receptors (2.10%) was considerably higher than the overall LoF frequency in human genome (0.16%). In particular, molecular evolutionary rates of candidate sour (14.7%) and bitter (1.8%) receptors were far higher in humans than those of sweet (0.02%), salty (0.05%), and umami (0.17%) receptors compared with other carnivorous mammals, although not all of the taste receptors were identified. Many LoF variants are population-specific, some of which arose even after population differentiation, not before divergence of the modern and archaic human. I conclude that modern humans might have been losing some sour and bitter receptor genes because of high-frequency LoF variants.

Longitudinal analysis of calorie restriction on rat taste bud morphology and expression of sweet taste modulators.

Calorie restriction (CR) is a lifestyle intervention employed to reduce body weight and improve metabolic functions primarily via reduction of ingested carbohydrates and fats. Taste perception is highly related to functional metabolic status and body adiposity. We have previously shown that sweet taste perception diminishes with age; however, relatively little is known about the effects of various lengths of CR upon taste cell morphology and function. We investigated the effects of CR on taste bud morphology and expression of sweet taste-related modulators in 5-, 17-, and 30-month-old rats. In ad libitum (AL) and CR rats, we consistently found the following parameters altered significantly with advancing age: reduction of taste bud size and taste cell numbers per taste bud and reduced expression of sonic hedgehog, type 1 taste receptor 3 (T1r3), α-gustducin, and glucagon-like peptide-1 (GLP-1). In the oldest rats, CR affected a significant reduction of tongue T1r3, GLP-1, and α-gustducin expression compared with age-matched AL rats. Leptin receptor immunopositive cells were elevated in 17- and 30-month-old CR rats compared with age-matched AL rats. These alterations of sweet taste-related modulators, specifically during advanced aging, suggest that sweet taste perception may be altered in response to different lengths of CR.

Diet-induced obesity reduces the responsiveness of the peripheral taste receptor cells.

INTRODUCTION: Obesity is a growing epidemic that causes many serious health related complications. While the causes of obesity are complex, there is conclusive evidence that overconsumption coupled with a sedentary lifestyle is the primary cause of this medical condition. Dietary consumption is controlled by appetite which is in turn regulated by multiple neuronal systems, including the taste system. However, the relationship between taste and obesity has not been well defined. Growing evidence suggests that taste perception in the brain is altered in obese animals and humans, however no studies have determined if there are altered taste responses in the peripheral taste receptor cells, which is the initiation site for the detection and perception of taste stimuli. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used C57Bl/6 mice which readily become obese when placed on a high fat diet. After ten weeks on the high fat diet, we used calcium imaging to measure how taste-evoked calcium signals were affected in the obese mice. We found that significantly fewer taste receptor cells were responsive to some appetitive taste stimuli while the numbers of taste cells that were sensitive to aversive taste stimuli did not change. Properties of the taste-evoked calcium signals were also significantly altered in the obese mice. Behavioral analyses found that mice on the high fat diet had reduced ability to detect some taste stimuli compared to their littermate controls. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that diet-induced obesity significantly influences peripheral taste receptor cell signals which likely leads to changes in the central taste system and may cause altered taste perception.