Gustatory Signals Research Articles

Sonic hedgehog binds to Patched molecules on sensory stem cells to initiate smell and taste function

Smell and taste function are tripartite systems involving sensory receptors, nerves and brain. Pathological changes in these systems depend primarily on impaired receptor function. Receptors in these systems are unique in that they contain neither blood vessels nor lymphatics and do not exhibit mitosis. For their growth and development, sensory receptors depend upon stem cell stimulation with growth/transcription factors secreted into saliva for taste and nasal mucus for smell. There are many of these growth/transcription factors but one of the major ones is sonic hedgehog (SHH) which causes receptor growth and development. Many pathological entities inhibit smell and taste function and do so by inhibition of these growth/transcription factors including SHH. Treatment with phosphodiesterase inhibitors activates SHH secretion which corrects these various pathologies. However, the molecular mechanism by which SHH acts on these stem cells to activate them is unclear. Recent studies have demonstrated that the efficacy of SHH at a molecular level depends upon its binding to two Patched molecules at a distinct site on the cell membrane of these sensory stem cells. This binding yields a signaling competent complex which, in the taste and smell systems, initiate growth and perpetuation of olfactory and gustatory receptors and results in their growth and development. This binding initiates the olfactory and gustatory signals which initiate smell and taste function.Support or Funding InformationThis institution did not receive any funding from agencies in the public, commercial, or not‐for‐profit sectors.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Differential Effects of Continuous versus Intermittent Dietary Fat Intake on Markers of Serotonin Signaling in the Circumvallate Papillae of the Tongue

Taste is a primary sensory modality that guides organisms in their determination of food preferences. Previous studies suggest that orosensory fat sensing may contribute to the intake and preference of dietary fat leading to the development of obesity. CD36 is the proposed fat taste receptor on the circumvallate papillae (CV) of the tongue and mediates fat sensing. Fat signaling via CD36 on the CV involves the regulation of serotonin (5‐HT) in taste receptor cells and activation of gustatory afferent nerves. The aim of these experiments was to investigate the effects of dietary fat intake on 5‐HT signaling in the CV using two feeding paradigms: continuous access to high fat diet (HFD) vs. limited access to dietary fat. We hypothesized that consumption of dietary fat, in specific patterns, contributes to the decreased sensitivity (i.e. hyposensitivity) of fat sensing through 5‐HT signaling dysregulation. The first experiment investigated the effects of continuous access to either a HFD or a low fat diet (LFD) for 1, 3 or 14 days on 5‐HT signaling in the CV. The second experiment investigated the effects of limited daily and intermittent access to dietary fat on 5‐HT signaling in the CV. Body weight and kilocalorie intake were assessed. In the CV, expression levels of CD36, 5‐HT1A, SERT, TPH1, and TPH2 mRNA were determined by Real Time PCR. Continuous HFD consumption for 14 days increased CD36, 5‐HT1A and SERT mRNA expression on the CV, suggesting reduced lingual fat sensing via decreased gustatory signaling from taste receptor cells. Limited, daily access to dietary fat increased CD36 and TPH1 mRNA expression on the CV suggesting enhanced lingual fat sensing compared to chow fed controls. Limited, intermittent access to dietary led to an escalation of fat intake without significant alterations in lingual expression of 5‐HT signaling. These data suggest that different patterns of fat consumption differentially affect 5‐HT signaling in the CV and that continuous access to HFD may lead to decreased orosensory fat perception by altering 5‐HT signaling in taste receptors cells.Support or Funding InformationLSUHSC to SDPThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Recognizing Taste: Coding Patterns Along the Neural Axis in Mammals.

The gustatory system encodes information about chemical identity, nutritional value, and concentration of sensory stimuli before transmitting the signal from taste buds to central neurons that process and transform the signal. Deciphering the coding logic for taste quality requires examining responses at each level along the neural axis-from peripheral sensory organs to gustatory cortex. From the earliest single-fiber recordings, it was clear that some afferent neurons respond uniquely and others to stimuli of multiple qualities. There is frequently a "best stimulus" for a given neuron, leading to the suggestion that taste exhibits "labeled line coding." In the extreme, a strict "labeled line" requires neurons and pathways dedicated to single qualities (e.g., sweet, bitter, etc.). At the other end of the spectrum, "across-fiber," "combinatorial," or "ensemble" coding requires minimal specific information to be imparted by a single neuron. Instead, taste quality information is encoded by simultaneous activity in ensembles of afferent fibers. Further, "temporal coding" models have proposed that certain features of taste quality may be embedded in the cadence of impulse activity. Taste receptor proteins are often expressed in nonoverlapping sets of cells in taste buds apparently supporting "labeled lines." Yet, taste buds include both narrowly and broadly tuned cells. As gustatory signals proceed to the hindbrain and on to higher centers, coding becomes more distributed and temporal patterns of activity become important. Here, we present the conundrum of taste coding in the light of current electrophysiological and imaging techniques at several levels of the gustatory processing pathway.

Dietary Verbascoside Influences Gut Morphology and the Expression of α-Transducin and α-Gustducin in the Small Intestine of Weaned Piglets Exposed to n-6 Polyunsaturated Fatty Acids-Induced Oxidative Stress.

Simple SummaryIn recent years, feed interventions with natural antioxidants have grown because oxidative stress is linked to the development of several diseases in pigs. Weaning is one of the most stressful events in pig breeding, inducing physiological, environmental, and social changes. These cause intestinal disorder, inflammation and oxidative stress that result in reduced pig health and growth. Previous data reported that dietary supplementation with a natural extract containing verbascoside positively affects piglets’ health and welfare by reducing oxidative stress parameters. This study shows that verbascoside protects the gastrointestinal tract from oxidative stress and may have an appetite-stimulatory effect by modulating gastrointestinal taste receptors’ related protein expression.Reducing oxidative stress is an important goal in post-weaning piglets; previous studies have reported that verbascoside decreases oxidative stress in piglets. The effect of verbascoside on gut morphology and α-transducin and α-gustducin expression in weaned piglets fed high dosages of sunflower oil, inducing oxidative stress, was evaluated. A diet with 9% sunflower oil (T1), the same diet supplemented with 5 mg of verbascoside/kg feed (T2) and a diet containing starch (control—CTR) were employed. Histology, histometry, histochemistry, immunofluorescence and Western blot analyses were performed on the piglets’ small intestine. In the T1 group, apical erosion was observed and villi height was lower than in other groups. The mucin profile was acidic in goblet cells of both the T1 and T2 groups. However, it was both neutral and acidic in the CTR group. Dietary treatments did not affect α-gustducin expression. Otherwise, the expression of α-transducin in the duodenum was lower (p < 0.01) in the T1 groups than in the other groups. The colocalization of α-transducin with chromogranin A and ghrelin revealed that the endocrine cells were immunopositive for both ghrelin and α-transducin. Overall, these results provide new insights into gut sensory perception in piglets and contribute to understanding how feed ingredients such as fat and polyphenols may be involved in gustatory signal transduction.

SU55 - FETAL ALCOHOL EXPOSURE IN RATS LEADS TO LONG-TERM CHANGES IN DNA METHYLATION PATTERNS OF TASTE-RELATED GENES IN POSTNATAL TONGUE

Background Considerable evidence indicates that there are potential long-term consequences of maternal alcohol consumption. Such exposures can lead to postnatal changes in the formation and function of brain circuits involved in learning, memory, and reward processing, and increase subsequent risks of alcohol abuse in later life. Although much interest has focused on the central areas affected by such exposures, less attention has been paid to the effects such exposures produce in the peripheral gustatory system. Here, we studied the potential molecular adaptations produced by fetal alcohol exposure in the postnatal chemosensory system by studying DNA methylation changes in Circumvallate Papillae (CV) taste cells in postnatal rats. Methods Pregnant Long Evans rats were divided into two weight-matched groups. Within each group the dams were randomly assigned to one of two dietary treatments (ET: ethanol, FCL: free choice liquid). Dams in the ET group were given ad libitum access to a liquid ethanol containing diet, with increasing amounts of ethanol between gestational (G) days 6–10, and full strength dose during G11-20. In the full strength diet, ethanol provided 35% of an animal's daily calories. Moreover, the timing of these administrations also exposed the fetus to ethanol during the developmental period (G11–20) of olfactory and orosensory systems. After delivery, rats born to dams in the ET group or the FCL group were chosen at random and sacrificed during mid-adolescence at P42. DNA samples were isolated from the CV of tongues, followed by genome-wide differential methylation analysis using the Rat Methyl-Seq DMR Capture kit (Agilent) and Illumina NexteraXT sequencing protocol. Results Differentially methylated cytosine residues were observed within and at the promoter regions of a large amount of olfactory receptor, taste receptor, oral-irritation, and gustatory signal transduction genes. Detailed examination of the methylation patterns of oro-sensory genes revealed interesting features of alternation. We also tested the ability of Partial Least Squares Discriminant Analysis (PLS-DA) to identify specific cytosine residues that could separate the two groups of ET and FCL prenatal-exposed rats. This indicated that cytosine resides with the most distinguishing power appeared to be located in close proximity to each other, corroborating the Runs test results. Thus, prenatal ET exposure could lead to the formation of cis-acting methylation blocks that strongly regulate or coordinate the expression of chemosensory-related genes, and fundamentally alter taste perception and taste preferences. Furthermore, pathway analysis revealed enrichment of genes involved in signal transduction pathways and epigenetic modification pathways, including genes such as Grm3, S1pr1, Prkacb, Hdac7 and Kcnmb4. Discussion Our results are the first evidences indicating that in addition to central nerves system effects, fetal alcohol exposure induced alcohol preference in later life could also be produced by altered patterns of DNA methylation in the peripheral gustatory system, via dysregulated expression of oro-sensory-related genes.

Fatty Acid Lingual Application Activates Gustatory and Reward Brain Circuits in the Mouse.

The origin of spontaneous preference for dietary lipids in humans and rodents is debated, though recent compelling evidence has shown the existence of fat taste that might be considered a sixth taste quality. We investigated the implication of gustatory and reward brain circuits, triggered by linoleic acid (LA), a long-chain fatty acid. The LA was applied onto the circumvallate papillae for 30 min in conscious C57BL/6J mice, and neuronal activation was assessed using c-Fos immunohistochemistry. By using real-time reverse transcription polymerase chain reaction (RT-qPCR), we also studied the expression of mRNA encoding brain-derived neurotrophic factor (BDNF), Zif-268, and Glut-1 in some brain areas of these animals. LA induced a significant increase in c-Fos expression in the nucleus of solitary tract (NST), parabrachial nucleus (PBN), and ventroposterior medialis parvocellularis (VPMPC) of the thalamus, which are the regions known to be activated by gustatory signals. LA also triggered c-Fos expression in the central amygdala and ventral tegmental area (VTA), involved in food reward, in conjunction with emotional traits. Interestingly, we noticed a high expression of BDNF, Zif-268, and Glut-1 mRNA in the arcuate nucleus (Arc) and hippocampus (Hipp), where neuronal activation leads to memory formation. Our study demonstrates that oral lipid taste perception might trigger the activation of canonical gustatory and reward pathways.

Short-Term Exposure to a Calorically Dense Diet Alters Taste-Evoked Responses in the Chorda Tympani Nerve, But Not Unconditioned Lick Responses to Sucrose.

Upon presentation of a calorically dense diet, rats display hyperphagia driven by increased meal size. The increased meal size and hyperphagia are most robust across the first several days of diet exposure before changes in body weight are evident, thus it is plausible that one of the factors that drives the hyperphagia may be enhanced orosensory responsivity. Here, electrophysiological responses to an array of taste stimuli were recorded from the chorda tympani nerve, a branch of the facial nerve that innervates taste receptors in the anterior tongue, of rats presented a high-energy (45% fat and 17% sucrose) diet for 3 days. Responses in the high-energy diet group were significantly higher for 0.01, 0.03, 0.06 and 0.3 M sucrose; 0.05 M Na-saccharin; and 0.01 M quinine compared with those of chow-fed controls. Another cohort of animals was tested in 30-min brief-access taste sessions (10-s trials) to a sucrose concentration series across the first 6 days of high-energy diet presentation. Both groups responded in a concentration-dependent manner. No significant group differences in unconditioned licking or trials initiated were revealed. Results from a third cohort of rats showed that responses to sucrose in a brief-access taste test also remained largely unchanged as a function of 3-day access to a sucrose solution. Taken together, these findings suggest that 3 days of high-energy diet exposure results in alterations to peripheral gustatory signaling yet these changes do not necessarily generalize to changes in responsiveness to sucrose, as least as measured in this procedure.

The Role of Neuropeptides in Peripheral Taste Signaling

Chemesthesis, the general chemical sensitivity of the skin and mucus membranes in the oronasal cavities and being perceived as pungency, irritation or heat, impacts taste responsiveness. The modulation of taste nerve responses is thought to be produced indirectly, via stimulation of peripheral sensory nerve terminals that have ability to release stored transmitters, e.g., calcitonin gene‐related peptide (CGRP) and substance P (SP), onto taste cells implying playing a role in gustatory signaling, by the functions of somatosensory neurons. The underlying assumption has been that neuropeptides exert their effects on taste transmitter secretion in taste buds of mice, a well‐accepted model for studying taste bud functions, as theoretically may relate to the processing of the gustatory information. Indeed, CGRP shapes peripheral taste signals via serotonergic signaling. In this study, using a combination of Ca2+ imaging with cellular biosensors – genetically‐engineered Chinese Hamster Ovary (CHO) cells, transgenic mice expressing green fluorescent protein (GFP) in the specific taste cell type and immunostaining, we showed that the net effect of SP reduced taste‐evoked ATP secretion from mouse taste buds. Specifically, SP elicited phospholipase C (PLC) activation‐dependent intracellular Ca2+ transients in taste cells via neurokinin 1 (NK1) receptors, most likely on glutamate‐aspartate transporter (GLAST)‐expressing Type I cells. Recently, γ‐aminobutyric acid (GABA) as well as the associated synthetic enzyme have been identified in Type I cells. Consequently, Type I cells secrete GABA in respond to SP. Combined with the recent findings that GABA provides negative paracrine feedback onto Receptor (Type II) cells by activating GABAA and/or GABAB receptors and reducing taste‐evoked ATP secretion, our results showed that taste‐evoked ATP secretion from intact taste buds, which remain cell‐cell communication intact, was reduced when SP was co‐applied with taste stimuli in the bath medium. We conclude that SP plays a role as an inhibitory transmitter that shapes peripheral taste signals via GABAergic signaling during processing gustatory information in taste buds. This seemingly tangled complex represents a new concept of taste signaling and that neuropeptides released from afferent sensory terminals play a regulatory role in processing taste signals.Support or Funding InformationAAA Fellows Grant Award Program Research Seed Grant to AYH (AAA‐3419).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Salt an Essential Nutrient: Advances in Understanding Salt Taste Detection Using Drosophila as a Model System.

Taste modalities are conserved in insects and mammals. Sweet gustatory signals evoke attractive behaviors while bitter gustatory information drive aversive behaviors. Salt (NaCl) is an essential nutrient required for various physiological processes, including electrolyte homeostasis, neuronal activity, nutrient absorption, and muscle contraction. Not only mammals, even in Drosophila melanogaster, the detection of NaCl induces two different behaviors: Low concentrations of NaCl act as an attractant, whereas high concentrations act as repellant. The fruit fly is an excellent model system for studying the underlying mechanisms of salt taste due to its relatively simple neuroanatomical organization of the brain and peripheral taste system, the availability of powerful genetic tools and transgenic strains. In this review, we have revisited the literature and the information provided by various laboratories using invertebrate model system Drosophila that has helped us to understand NaCl salt taste so far. We hope that this compiled information from Drosophila will be of general significance and interest for forthcoming studies of the structure, function, and behavioral role of NaCl-sensitive (low and high concentrations) gustatory circuitry for understanding NaCl salt taste in all animals.

Olfactory cues play a significant role in removing fungus from the body surface of Drosophila melanogaster.

Many insects and Dipterans in particular are known to spend considerable time grooming, but whether these behaviors actually are able to remove pathogenic fungal conidia is less clear. In this study, we examined whether grooming serves to protect flies by reducing the risk of fungal infection in Drosophila melanogaster. First, we confirmed that fungi were removed by grooming. Entomopathogenic, opportunistic, and plant pathogenic fungi were applied on the body surface of the flies. To estimate grooming efficiency, the number of removal conidia through grooming was quantified and we successfully demonstrated that flies remove fungal conidia from their body surfaces via grooming behavior. Second, the roles of gustatory and olfactory signals in fungus removal were examined. The wildtype fly Canton-S, the taste deficiency mutant poxn 70, and the olfactory deficiency mutant orco1 were used in the tests. Comparisons between Canton-S and poxn 70 flies indicated that gustatory signals do not have a significant role in fungal removal via grooming behavior in D. melanogaster. In contrast, the efficiency of conidia removal in orco1 flies was drastically decreased. Consequently, this study indicated that flies rely on mechanical stimulus for the induction of grooming and olfaction for more detailed removal.

The gram-negative sensing receptor PGRP-LC contributes to grooming induction in Drosophila.

Behavioral resistance protects insects from microbial infection. However, signals inducing insect hygiene behavior are still relatively unexplored. Our previous study demonstrated that olfactory signals from microbes enhance insect hygiene behavior, and gustatory signals even induce the behavior. In this paper, we postulated a cross-talk between behavioral resistance and innate immunity. To examine this hypothesis, we employed a previously validated behavioral test to examine the function of taste signals in inducing a grooming reflex in decapitated flies. Microbes, which activate different pattern recognition systems upstream of immune pathways, were applied to see if there was any correlation between microbial perception and grooming reflex. To narrow down candidate elicitors, the grooming induction tests were conducted with highly purified bacterial components. Lastly, the role of DAP-type peptidoglycan in grooming induction was confirmed. Our results demonstrate that cleaning behavior can be triggered through recognition of DAP-type PGN by its receptor PGRP-LC.

Processing of Intraoral Olfactory and Gustatory Signals in the Gustatory Cortex of Awake Rats

Processing of Intraoral Olfactory and Gustatory Signals in the Gustatory Cortex of Awake Rats

Convergent gustatory and viscerosensory processing in the human dorsal mid-insula.

The homeostatic regulation of feeding behavior requires an organism to be able to integrate information from its internal environment, including peripheral visceral signals about the body's current energy needs, with information from its external environment, such as the palatability of energy-rich food stimuli. The insula, which serves as the brain's primary sensory cortex for representing both visceral signals from the body and taste signals from the mouth and tongue, is a likely candidate region in which this integration might occur. However, to date it has been unclear whether information from these two homeostatically critical faculties is merely co-represented in the human insula, or actually integrated there. Recent functional neuroimaging evidence of a common substrate for visceral interoception and taste perception within the human dorsal mid-insula suggests a model whereby a single population of neurons may integrate viscerosensory and gustatory signals. To test this model, we used fMRI-Adaptation to identify whether insula regions that exhibit repetition suppression following repeated interoception trials would then also exhibit adapted responses to subsequent gustatory stimuli. Multiple mid and anterior regions of the insula exhibited adaptation to interoceptive trials specifically, but only the dorsal mid-insula regions exhibited an adapted gustatory response following interoception. The discovery of this gustatory-interoceptive convergence within the neurons of the human insula supports the existence of a heretofore-undocumented neural pathway by which visceral signals from the periphery modulate the activity of brain regions involved in feeding behavior. Hum Brain Mapp 38:2150-2164, 2017. © 2017 Wiley Periodicals, Inc.

Processing of Intraoral Olfactory and Gustatory Signals in the Gustatory Cortex of Awake Rats.

Food perception and choice depend upon the concurrent processing of olfactory and gustatory signals from the mouth. The primary gustatory cortex has been proposed to integrate chemosensory stimuli; however, no study has examined the single-unit responses to intraoral odorant presentation. Here we found that neurons in gustatory cortex can respond either exclusively to tastants, exclusively to odorants, or to both (bimodal). Several differences exist between these groups' responses; notably, bimodal neurons code palatability significantly better than unimodal neurons. This group of neurons might represent a substrate for how odorants gain the quality of tastants.

Organization of olfactory centres in the malaria mosquito Anopheles gambiae.

Mosquitoes are vectors for multiple infectious human diseases and use a variety of sensory cues (olfactory, temperature, humidity and visual) to locate a human host. A comprehensive understanding of the circuitry underlying sensory signalling in the mosquito brain is lacking. Here we used the Q-system of binary gene expression to develop transgenic lines of Anopheles gambiae in which olfactory receptor neurons expressing the odorant receptor co-receptor (Orco) gene are labelled with GFP. These neurons project from the antennae and maxillary palps to the antennal lobe (AL) and from the labella on the proboscis to the suboesophageal zone (SEZ), suggesting integration of olfactory and gustatory signals occurs in this brain region. We present detailed anatomical maps of olfactory innervations in the AL and the SEZ, identifying glomeruli that may respond to human body odours or carbon dioxide. Our results pave the way for anatomical and functional neurogenetic studies of sensory processing in mosquitoes.

Acid-sensing ion channels and transient-receptor potential ion channels in zebrafish taste buds

Sensory information from the environment is required for life and survival, and it is detected by specialized cells which together make up the sensory system. The fish sensory system includes specialized organs that are able to detect mechanical and chemical stimuli. In particular, taste buds are small organs located on the tongue in terrestrial vertebrates that function in the perception of taste. In fish, taste buds occur on the lips, the flanks, and the caudal (tail) fins of some species and on the barbels of others. In fish taste receptor cells, different classes of ion channels have been detected which, like in mammals, presumably participate in the detection and/or transduction of chemical gustatory signals. However, since some of these ion channels are involved in the detection of additional sensory modalities, it can be hypothesized that taste cells sense stimuli other than those specific for taste. This mini-review summarizes current knowledge on the presence of transient-receptor potential (TRP) and acid-sensing (ASIC) ion channels in the taste buds of teleosts, especially adult zebrafish. Up to now ASIC4, TRPC2, TRPA1, TRPV1 and TRPV4 ion channels have been found in the sensory cells, while ASIC2 was detected in the nerves supplying the taste buds.

Social Experience Is Sufficient to Modulate Sleep Need of Drosophila without Increasing Wakefulness.

Organisms quickly learn about their surroundings and display synaptic plasticity which is thought to be critical for their survival. For example, fruit flies Drosophila melanogaster exposed to highly enriched social environment are found to show increased synaptic connections and a corresponding increase in sleep. Here we asked if social environment comprising a pair of same-sex individuals could enhance sleep in the participating individuals. To study this, we maintained individuals of D. melanogaster in same-sex pairs for a period of 1 to 4 days, and after separation, monitored sleep of the previously socialized and solitary individuals under similar conditions. Males maintained in pairs for 3 or more days were found to sleep significantly more during daytime and showed a tendency to fall asleep sooner as compared to solitary controls (both measures together are henceforth referred to as “sleep-enhancement”). This sleep phenotype is not strain-specific as it is observed in males from three different “wild type” strains of D. melanogaster. Previous studies on social interaction mediated sleep-enhancement presumed ‘waking experience’ during the interaction to be the primary underlying cause; however, we found sleep-enhancement to occur without any significant increase in wakefulness. Furthermore, while sleep-enhancement due to group-wise social interaction requires Pigment Dispersing Factor (PDF) positive neurons; PDF positive and CRYPTOCHROME (CRY) positive circadian clock neurons and the core circadian clock genes are not required for sleep-enhancement to occur when males interact in pairs. Pair-wise social interaction mediated sleep-enhancement requires dopamine and olfactory signaling, while visual and gustatory signaling systems seem to be dispensable. These results suggest that socialization alone (without any change in wakefulness) is sufficient to cause sleep-enhancement in fruit fly D. melanogaster males, and that its neuronal control is context-specific.

The Gustatory Signaling Pathway and Bitter Taste Receptors Affect the Development of Obesity and Adipocyte Metabolism in Mice.

Intestinal chemosensory signaling pathways involving the gustatory G-protein, gustducin, and bitter taste receptors (TAS2R) have been implicated in gut hormone release. Alterations in gut hormone profiles may contribute to the success of bariatric surgery. This study investigated the involvement of the gustatory signaling pathway in the development of diet-induced obesity and the therapeutic potential of targeting TAS2Rs to induce body weight loss. α-gustducin-deficient (α-gust-/-) mice became less obese than wild type (WT) mice when fed a high-fat diet (HFD). White adipose tissue (WAT) mass was lower in α-gust-/- mice due to increased heat production as a result of increases in brown adipose tissue (BAT) thermogenic activity, involving increased protein expression of uncoupling protein 1. Intra-gastric treatment of obese WT and α-gust-/- mice with the bitter agonists denatonium benzoate (DB) or quinine (Q) during 4 weeks resulted in an α-gustducin-dependent decrease in body weight gain associated with a decrease in food intake (DB), but not involving major changes in gut peptide release. Both WAT and 3T3-F442A pre-adipocytes express TAS2Rs. Treatment of pre-adipocytes with DB or Q decreased differentiation into mature adipocytes. In conclusion, interfering with the gustatory signaling pathway protects against the development of HFD-induced obesity presumably through promoting BAT activity. Intra-gastric bitter treatment inhibits weight gain, possibly by directly affecting adipocyte metabolism.

A gustatory receptor tuned to d-fructose in antennal sensilla chaetica of Helicoverpa armigera

Insect gustatory systems play important roles in food selection and feeding behaviors. In spite of the enormous progress in understanding gustation in Drosophila, for other insects one of the key elements in gustatory signaling, the gustatory receptor (GR), is still elusive. In this study, we report that fructose elicits behavioral and physiological responses in Helicoverpa armigera (Harm) to fructose and identify the gustatory receptor for this sugar. Using the proboscis extension reflex (PER) assays we found that females respond to fructose following stimulation of the distal part of the antenna, where we have identified contact chemosensilla tuned to fructose in tip recording experiments. We isolated three full-length cDNAs encoding candidate HarmGRs based on comparison with orthologous GR sequences in Heliothis virescens and functionally characterized the responses of HarmGR4 to 15 chemicals when this receptor was expressed in Xenopus oocytes with two-electrode voltage-clamp recording. Among the tastants tested, the oocytes dose-dependently responded only to d-fructose (EC50 = 0.045 M). By combining behavioral, electrophysiological and molecular approaches, these results provide basic knowledge for further research on the molecular mechanisms of gustatory reception.

Central connectivity of the chorda tympani afferent terminals in the rat rostral nucleus of the solitary tract.

The rostral nucleus of the solitary tract (rNST) receives gustatory input via chorda tympani (CT) afferents from the anterior two-thirds of the tongue and transmits it to higher brain regions. To help understand how the gustatory information is processed at the 1st relay nucleus of the brain stem, we investigated the central connectivity of the CT afferent terminals in the central subdivision of the rat rNST through retrograde labeling with horseradish peroxidase, immunogold staining for GABA, glycine, and glutamate, and quantitative ultrastructural analysis. Most CT afferents were small myelinated fibers (<5µm(2) in cross-sectional area) and made simple synaptic arrangements with 1-2 postsynaptic dendrites. It suggests that the gustatory signal is relayed to a specific group of neurons with a small degree of synaptic divergence. The volume of the identified synaptic boutons was positively correlated with their mitochondrial volume and active zone area, and also with the number of their postsynaptic dendrites. One-fourth of the boutons received synapses from GABA-immunopositive presynaptic profiles, 27% of which were also glycine-immunopositive. These results suggest that the gustatory information mediated by CT afferents to the rNST is processed in a simple and specific manner. They also suggest that the minority of CT afferents are presynaptically modulated by GABA- and/or glycine-mediated mechanism.