Sweet Taste Receptor Signaling Network: Possible Implication for Cognitive Functioning

Sweet taste receptors are transmembrane protein network specialized in the transmission of information from special “sweet” molecules into the intracellular domain. These receptors can sense the taste of a range of molecules and transmit the information downstream to several acceptors, modulate cell specific functions and metabolism, and mediate cell-to-cell coupling through paracrine mechanism. Recent reports indicate that sweet taste receptors are widely distributed in the body and serves specific function relative to their localization. Due to their pleiotropic signaling properties and multisubstrate ligand affinity, sweet taste receptors are able to cooperatively bind multiple substances and mediate signaling by other receptors. Based on increasing evidence about the role of these receptors in the initiation and control of absorption and metabolism, and the pivotal role of metabolic (glucose) regulation in the central nervous system functioning, we propose a possible implication of sweet taste receptor signaling in modulating cognitive functioning.

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The effects of sweeteners and sweetness enhancers on obesity and diabetes: a review

Journal of Food Bioactives ◽

10.31665/jfb.2018.4166 ◽

2018 ◽

Vol 4 ◽

Cited By ~ 2

Author(s):

Yanli Jiao ◽

Yu Wang

Keyword(s):

Metabolic Regulation ◽

Hormone Secretion ◽

Taste Receptor ◽

Caloric Intake ◽

Sweet Taste ◽

The Body ◽

Incretin Hormone ◽

Obesity And Diabetes ◽

Sweet Taste Receptors

Sweet taste, one of the five basic taste qualities, is not only important for evaluation of food quality, but also guides the dietary food choices of animals. Sweet taste involves a variety of chemical compounds and structures, including natural sugars, sugar alcohols, natural and artificial sweeteners, and sweet-tasting proteins. The preference for sweetness has induced the over-consumption of sugar, contributing to certain prevailing health problems, such as obesity, diabetes and cardiovascular disease. Non-nutritive sweeteners, including natural and synthetic sweeteners, and sweet-tasting proteins have been added to foods to reduce the caloric intake from sugar, but many of these sugar substitutes induce an off-taste or after taste that negatively impacts any pleasure derived from the sweet taste. Sweet taste is detected by sweet taste receptor, that also play an important role in the metabolic regulation of the body, such as glucose homeostasis and incretin hormone secretion. In this review, the role of sweet tastants and the sweet taste receptors involved in sweetness perception, and their effect on obesity and diabetes are summarized. Sweet taste enhancement, as a new way to solve the over-consumption of sugar, is discussed in this contribution. Sweet taste enhancers can bind with sweet tastans to potentiate the sweetness of food without producing any taste by itself. Various type of sweet taste enhancers, including synthetic compounds, food-processed substances and aroma compounds, are summarized. Notably, few natural, non-volatile compounds have been identified as sweetness enhancers.

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Drosophila sweet taste receptor

Pure and Applied Chemistry ◽

10.1351/pac200274071159 ◽

2002 ◽

Vol 74 (7) ◽

pp. 1159-1165 ◽

Cited By ~ 3

Author(s):

Kunio Isono ◽

Kohei Ueno ◽

Masayuki Ohta ◽

Hiromi Morita

Keyword(s):

Taste Receptor ◽

Sweet Taste ◽

P Element ◽

Taste Receptors ◽

Wild Populations ◽

Intracellular Loop ◽

Sweet Taste Receptor ◽

Loop Domain ◽

Sweet Taste Receptors ◽

Receptor Family

Like the Sac locus controlling sugar sensitivity in mice, the taste gene Tre of the fruitfly Drosophila was discovered in wild populations as a genetic dimorphism controlling gustatory sensitivity to a sugar trehalose. By activating a P-element transposon near the gene locus we obtained induced Tre mutations and analyzed the associated changes in gene organizations and the mRNA expressions. The analysis showed that Tre is identical to Gr5a, a gene that belongs to a novel seven-transmembrane receptor family expressed in chemosensory neurons and predicted to encode chemosensory receptors. Thus, Gr5a is a candidate sweet taste receptor in the fly. An amino acid substitution in the second intracellular loop domain was identified to be functionally correlated with the genetic dimorphism of Tre. Since Tre controls sweet taste sensitivity to a limited subset of sugars, other Gr genes phylogenetically related to Tre may also encode sweet taste receptors. Those candidate sweet taste receptors, however, are phylogenetically distinct from vertebrate sweet taste receptors, suggesting that the sweet taste receptors in animals do not share a common origin.

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Taste sensations: history of study, evolutionary feasibility and strategies for forming correct taste preferences in children

Medical Council ◽

10.21518/2079-701x-2020-10-65-73 ◽

2020 ◽

pp. 65-73

Author(s):

I. N. Zakharova ◽

Yu. A. Dmitrieva ◽

E. B. Machneva ◽

A. N. Tsutsaeva

Keyword(s):

Eating Disorders ◽

Human Health ◽

Taste Receptor ◽

Sweet Taste ◽

Food Selectivity ◽

Taste Preferences ◽

Taste Receptors ◽

Sweet Taste Receptor ◽

Sweet Taste Receptors ◽

History Of

Taste preferences influence not only the formation of human health, but also many areas of his life. That is why the problem of understanding the nature and regularities of taste formation has been a concern for scientists since ancient times and remains relevant nowadays. The article presents generalized data on the history of studying taste from the times of Ancient Greece to our time. Notions about the system of taste sensations in works of Aristotle, Galen, Avicenna, Vesaliy, other medieval scientists and researchers of New time are described. The authors also present an overview of current studies on the evolutionary appropriateness of taste sensations using the expression of sweet taste receptors in animals with different diets. It has been shown that obligate carnivorous animals have lost the function of sweet taste receptors, and in hummingbirds eating sweet floral nectar, on the contrary, another sweet taste receptor has acquired the function of a sweet taste receptor to detect sugars. The authors pay special attention to the available ways of forming correct taste preferences and overcoming eating disorders in infants, which is important from the point of view of the child’s future health. In particular, strategies for repeated taste effects of new foods as well as multisensory interactions with food, including sound, visual, olfactory, tactile and tasting effects are presented. It is particularly important to develop correct taste habits in children with eating disorders such as neophobia and food selectivity. Understanding the multifactorial nature of taste preferences and their impact on human health allows finding new strategies to «teach» taste from early childhood.

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Loss of sweet taste despite the conservation of sweet receptor genes in insectivorous bats

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2021516118 ◽

2021 ◽

Vol 118 (4) ◽

pp. e2021516118

Author(s):

Hengwu Jiao ◽

Huan-Wang Xie ◽

Libiao Zhang ◽

Nima Zhuoma ◽

Peihua Jiang ◽

...

Keyword(s):

Functional Divergence ◽

Receptor Gene ◽

Taste Receptor ◽

Sweet Taste ◽

Taste Perception ◽

Taste Receptors ◽

Behavioral Experiments ◽

Insectivorous Bats ◽

Sweet Taste Receptor ◽

Sweet Taste Receptors

The evolution of taste perception is usually associated with the ecology and dietary changes of organisms. However, the association between feeding ecology and taste receptor evolution is unclear in some lineages of vertebrate animals. One example is the sweet taste receptor gene Tas1r2. Previous analysis of partial sequences has revealed that Tas1r2 has undergone equally strong purifying selection between insectivorous and frugivorous bats. To test whether the sweet taste function is also important in bats with contrasting diets, we examined the complete coding sequences of both sweet taste receptor genes (Tas1r2 and Tas1r3) in 34 representative bat species. Although these two genes are highly conserved between frugivorous and insectivorous bats at the sequence level, our behavioral experiments revealed that an insectivorous bat (Myotis ricketti) showed no preference for natural sugars, whereas the frugivorous species (Rousettus leschenaultii) showed strong preferences for sucrose and fructose. Furthermore, while both sweet taste receptor genes are expressed in the taste tissue of insectivorous and frugivorous bats, our cell-based assays revealed striking functional divergence: the sweet taste receptors of frugivorous bats are able to respond to natural sugars whereas those of insectivorous bats are not, which is consistent with the behavioral preference tests, suggesting that functional evolution of sweet taste receptors is closely related to diet. This comprehensive study suggests that using sequence conservation alone could be misleading in inferring protein and physiological function and highlights the power of combining behavioral experiments, expression analysis, and functional assays in molecular evolutionary studies.

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Whole-Brain Mapping of the Expression Pattern of T1R2, a Subunit Specific to the Sweet Taste Receptor

Frontiers in Neuroanatomy ◽

10.3389/fnana.2021.751839 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jea Hwa Jang ◽

Ha Kyeong Kim ◽

Dong Woo Seo ◽

Su Young Ki ◽

Soonhong Park ◽

...

Keyword(s):

Central Nervous System ◽

Metabolic Regulation ◽

Taste Receptor ◽

Sweet Taste ◽

Taste Receptors ◽

Sweet Taste Receptor ◽

Sweet Taste Receptors ◽

The Central Nervous System ◽

A Subunit ◽

The Brain

Chemosensory receptors are expressed primarily in sensory organs, but their expression elsewhere can permit ligand detection in other contexts that contribute to survival. The ability of sweet taste receptors to detect natural sugars, sugar alcohols, and artificial sweeteners suggests sweet taste receptors are involved in metabolic regulation in both peripheral organs and in the central nervous system. Our limited knowledge of sweet taste receptor expression in the brain, however, has made it difficult to assess their contribution to metabolic regulation. We, therefore, decided to profile the expression pattern of T1R2, a subunit specific to the sweet taste receptor complex, at the whole-brain level. Using T1r2-Cre knock-in mice, we visualized the overall distribution of Cre-labeled cells in the brain. T1r2-Cre is expressed not only in various populations of neurons, but also in glial populations in the circumventricular organs and in vascular structures in the cortex, thalamus, and striatum. Using immunohistochemistry, we found that T1r2 is expressed in hypothalamic neurons expressing neuropeptide Y and proopiomelanocortin in arcuate nucleus. It is also co-expressed with a canonical taste signaling molecule in perivascular cells of the median eminence. Our findings indicate that sweet taste receptors have unidentified functions in the brain and suggest that they may be a novel therapeutic target in the central nervous system.

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Genetics of sweet taste preferences

Pure and Applied Chemistry ◽

10.1351/pac200274071135 ◽

2002 ◽

Vol 74 (7) ◽

pp. 1135-1140 ◽

Cited By ~ 15

Author(s):

Alexander A. Bachmanov ◽

Danielle R. Reed ◽

Xia Li ◽

Gary K. Beauchamp

Keyword(s):

Positional Cloning ◽

Inbred Mouse ◽

Taste Receptor ◽

Sweet Taste ◽

Mouse Strains ◽

Taste Receptors ◽

Chromosome 4 ◽

Sweet Taste Receptor ◽

Distal Chromosome ◽

Allelic Differences

Inbred mouse strains display marked differences in avidity for sweet solutions due in part to genetic differences among strains. Using several techniques, we have located a number of regions throughout the genome that influence sweetener acceptance. One prominent locus regulating differences in sweetener preferences among mouse strains is the saccharin preference (Sac) locus on distal chromosome 4. Afferent responses of gustatory nerves to sweeteners also vary as a function of allelic differences in the Sac locus, suggesting that this gene may encode a sweet taste receptor. Using a positional cloning approach, we identified a gene (Tas1r3) encoding the third member of the T1R family of putative taste receptors, T1R3. Introgression by serial back-crossing of a chromosomal fragment containing the Tas1r3 allele from the high sweetener-preferring strain onto the genetic background of the low sweetener-preferring strain rescued its low sweetener-preference phenotype. Tas1r3 has two common haplotypes, one found in mouse strains with elevated sweetener preference and the other in strains relatively indifferent to sweeteners. This study, in conjunction with complimentary recent studies from other laboratories, provides compelling evidence that Tas1r3 is equivalent to the Sac locus and that the T1R3 receptor (when co-expressed with taste receptor T1R2) responds to sweeteners. However, other sweetness receptors may remain to be identified.

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Expression of Taste Receptor 2 Subtypes in Human Testis and Sperm

Journal of Clinical Medicine ◽

10.3390/jcm9010264 ◽

2020 ◽

Vol 9 (1) ◽

pp. 264 ◽

Cited By ~ 2

Author(s):

Laura Governini ◽

Bianca Semplici ◽

Valentina Pavone ◽

Laura Crifasi ◽

Camilla Marrocco ◽

...

Keyword(s):

Taste Receptor ◽

Receptor Activation ◽

Taste Buds ◽

The Body ◽

Semen Parameters ◽

Human Testis ◽

Taste Receptors ◽

Organ Systems

Taste receptors (TASRs) are expressed not only in the oral cavity but also throughout the body, thus suggesting that they may play different roles in organ systems beyond the tongue. Recent studies showed the expression of several TASRs in mammalian testis and sperm, indicating an involvement of these receptors in male gametogenesis and fertility. This notion is supported by an impaired reproductive phenotype of mouse carrying targeted deletion of taste receptor genes, as well as by a significant correlation between human semen parameters and specific polymorphisms of taste receptor genes. To better understand the biological and thus clinical significance of these receptors for human reproduction, we analyzed the expression of several members of the TAS2Rs family of bitter receptors in human testis and in ejaculated sperm before and after in vitro selection and capacitation. Our results provide evidence for the expression of TAS2R genes, with TAS2R14 being the most expressed bitter receptor subtype in both testis tissue and sperm cells, respectively. In addition, it was observed that in vitro capacitation significantly affects both the expression and the subcellular localization of these receptors in isolated spermatozoa. Interestingly, α-gustducin and α-transducin, two Gα subunits expressed in taste buds on the tongue, are also expressed in human spermatozoa; moreover, a subcellular redistribution of both G protein α-subunits to different sub-compartments of sperm was registered upon in vitro capacitation. Finally, we shed light on the possible downstream transduction pathway initiated upon taste receptor activation in the male reproductive system. Performing ultrasensitive droplets digital PCR assays to quantify RNA copy numbers of a distinct gene, we found a significant correlation between the expression of TAS2Rs and TRPM5 (r = 0.87), the cation channel involved in bitter but also sweet and umami taste transduction in taste buds on the tongue. Even if further studies are needed to clarify the precise functional role of taste receptors for successful reproduction, the presented findings significantly extend our knowledge of the biological role of TAS2Rs for human male fertility.

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The Role of Bitter and Sweet Taste Receptors in Upper Airway Immunity

Current Allergy and Asthma Reports ◽

10.1007/s11882-015-0571-8 ◽

2015 ◽

Vol 15 (12) ◽

Cited By ~ 28

Author(s):

Alan D. Workman ◽

James N. Palmer ◽

Nithin D. Adappa ◽

Noam A. Cohen

Keyword(s):

Upper Airway ◽

Sweet Taste ◽

Taste Receptors ◽

Sweet Taste Receptors

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EXTRAORAL SWEET TASTE RECEPTORS IN RESPIRATORY SYSTEM

Medical academic journal ◽

10.17816/maj18127-33 ◽

2018 ◽

Vol 18 (1) ◽

pp. 27-33 ◽

Cited By ~ 2

Author(s):

V N Mineev ◽

P V Brukhanova ◽

D E Koksharova

Keyword(s):

Diabetes Mellitus ◽

Respiratory Tract ◽

Antimicrobial Peptides ◽

Respiratory System ◽

Clinical Medicine ◽

Sweet Taste ◽

Scientific Basis ◽

Taste Receptors ◽

Sweet Taste Receptors

The possible pathogenetic role of extraoral sweet taste receptors Tas1R in respiratory system is considered. In many respects, the function of extraoral receptors for sweet taste still remains unclear. The mechanism of intracellular signal transduction at sweet taste reception is considered, as well as the molecular mechanism of interaction of Tas2R and Tas1R receptors, expressed on the same cell. Tas1R receptors in respiratory system can function as a “rheostat” to control the amount of secretion of antimicrobial peptides that is mediated by extraoral bitter taste receptors Tas2R, depending on the concentration of glucose on the surface of the airways. In diabetes mellitus, the liquid on the luminal surface of respiratory tract contains an increased concentration of glucose, which leads to overexpression of TAS1R2 / TAS1R3, inhibition of Tas2R signaling activity and to decrease in secretion of antimicrobial peptides. Clinically, the effect on glucose homeostasis in the lumen of the respiratory tract with comorbid respiratory pathology, including diabetes mellitus, is considered. A possible sequence of pathogenetic mechanisms in respiratory system, associated with extraoral sweet taste receptors is presented as a vicious circle. Research into the problem of role of the ectopic chemosensory network in clinical medicine will bring new knowledge on the predisposition to diseases, a deeper understanding of the mechanisms of their development, and will serve as a scientific basis for developing new medicinal approaches.

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