Type 1 Taste Receptors in Taste and Metabolism
Total Page：16
File Type：pdf, Size：1020Kb
Sweetness: Developmental and Functional Effects Reprinted with permission from: Ann Nutr Metab 2017;70(suppl 3):27–36 DOI: 10.1159/000478760 Type 1 Taste Receptors in Taste and Metabolism Matthew Kochem Rutgers University Department of Nutritional Sciences, New Brunswick, NJ , USA Key Messages conditions stemming from overnutrition. Recent research • Type 1 taste receptors (T1Rs) guide the consumption has revealed that type 1 taste receptors (T1Rs), which are of sweet and savory foods. largely responsible for sweet and umami taste, may also in- • T1Rs are expressed in non-oral tissues, where they are fluence the absorption and metabolism of the foods we eat. thought to stimulate absorptive and hormonal Preliminary research shows that T1Rs contribute to intestinal responses to ingested foods. glucose absorption, blood sugar and insulin regulation, and • Mice lacking T1Rs are partially protected against the body’s responses to excessive energy intake. In light of diet-induced obesity and hyperinsulinemia. these findings, T1Rs have come to be understood as nutrient • Further research is needed to determine the effects of sensors, among other roles, that facilitate the selection, di- T1R activity on human health. gestion, and metabolism of foods. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel Introduction Keywords Type 1 taste receptors (T1Rs) in the mouth signal the Taste receptor · T1R · Sweet · Savory · Umami · Taste · presence of saccharides and amino acids [1, 2] . The abil- Perception · Glycemia · Insulin · Obesity ity to detect these nutrients underlies a critical set of psy- chological and physiological processes that ensure hu- man survival. T1Rs are largely responsible for the con- Abstract scious perception of the appetitive sweet and umami Our sense of taste allows us to evaluate the nutritive value of tastes, which guide food intake [3] . Taste receptors may foods prior to ingesting them. Sweet taste signals the pres- also regulate metabolic processes which promote efficient ence of sugars, and savory taste signals the presence of ami- digestion and assimilation of the foods we eat. no acids. The ability to identify these macronutrients in Taste perception allows us to evaluate the chemical foods was likely crucial for the survival of our species when makeup of foods in order to determine whether they con- nourishing food sources were sparse. In modern, industrial- tain nutrients and/or toxins. Savory (umami) taste per- ized settings, taste perception continues to play an impor- ception, primarily stimulated by glutamate and ribonu- tant role in human health as we attempt to prevent and treat cleotides, guides the consumption of protein sources. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel Matthew Kochem, PhD 1016 Howell Mill Road, Apt. 2410 Atlanta, GA 30318 (USA) E-Mail [email protected] E-Mail kochem @ scarletmail.rutgers.ed Umami taste Sweet taste Sweet IMP peptides HPS Glutamate GMP Saccharides T1R1 T1R3 T1R2 T1R3 Fig. 1. Type 1 taste receptor (T1R) subunits form heterodimers to bind sweet and umami compounds. IMP, ino- sine monophosphate; GMP, guanosine monophosphate; HPS, high-potency sweeteners. This helps to ensure the consumption of essential amino T1R Structure and Signaling acids, which cannot be synthesized by the body and must The umami and sweet taste receptors are heteromer- be obtained in the diet. Similarly, sweet taste perception ic, G-protein-coupled receptors ( Fig. 1 ). T1R1-T1R3 is ac- guides the intake of carbohydrate, a critical energy source tivated by glutamate and aspartate, as well as certain 5′- for the brain and other tissues. Considering the energy ribonucleotides, such as inosine and guanosine [1, 16] . demands of growth, it is unsurprising that infants and T1R2-T1R3 is activated by a diverse set of stimuli includ- children are innately and strongly attracted to sweet-tast- ing carbohydrates (mono- and disaccharides), sugar alco- ing compounds [4] . hols, sweet peptides and proteins, and other small mole- Taste receptors are also implicated in the regulation of cule sweeteners [16] . In rodents, T1r3 ablation drastically nutrient metabolism. Recent research shows that taste re- reduces neural and behavior responses to umami and ceptors are expressed not only in the oral cavity, but in sweet stimuli [3] . Interestingly, sweet and umami taste are metabolically active tissues throughout the body [5–13] . not entirely abolished in these animals, suggesting addi- The majority of this work has focused on the roles of in- tional sensors for these stimuli. The residual responses to testinal and pancreatic T1Rs in glucose metabolism. Data monosodium glutamate may be transduced by mGluRs from in vitro and animal studies suggest that taste recep- [17, 18] , and residual sweet responses may be transduced tors in the intestine and pancreas facilitate glucose ab- by components of the sodium potassium pump (Na+/ sorption and disposal [5, 14, 15] . Animals lacking T1Rs K+-ATPase), sodium-glucose linked transporter 1 display dramatically altered responses to food ingestion (SGLT1), and glucose transporters (GLUTs) in taste cells and respond differently to obesogenic diets. [19] . Because they participate in a host of processes involved T1Rs are expressed on taste cells, which are arranged in the consumption and metabolism of foods, taste recep- in groups called taste buds. Taste buds are distributed in tors may play a key part in our understanding of nutri- distinct loci throughout the oral cavity, each of which is tion-related diseases. This review will discuss the basic innervated by branches of the 7th, 9th, and 10th cranial functions of T1Rs, the importance of sweet and savory nerves [20] . Taste buds are found on the fungiform papil- taste, and the striking effects of taste receptors on metab- lae on the anterior tongue, the foliate and circumvallate olism and long-term health. papillae on the posterior tongue, and the smooth epithe- lia of the soft palate and the pharynx [20] . An often cited 28 Reprinted with permission from: Kochem Ann Nutr Metab 2017;70(suppl 3):27–36 DOI: 10.1159/000478760 but inaccurate belief is that specific regions of the oral and appetitive at low levels, especially when mixed with cavity are solely responsible for specific taste modalities sugar (such as in fruit) [25] . Bitter taste, which is aversive [21] . Although certain regions of the oral cavity are par- at high intensities and can induce nausea, is adaptive be- ticularly responsive to certain taste qualities, all taste mo- cause it deters us from consuming large quantities of tox- dalities can be elicited in all regions. Sweet and umami ins [26] . taste transduction begins when taste stimuli enter the The critical link between taste perception and food in- taste bud pore and bind T1Rs on taste cells, which are gestion is highlighted in patients with taste disorders. electrically active, specialized, epithelial cells. Taste re- Taste sensitivity can be partially lost (hypogeusia) or en- ceptor binding can activate GTP-binding proteins, which tirely lost (ageusia) due to various causes at the cellular begin the intracellular signaling cascade leading to taste and organ level stemming from aging, disease states, and cell depolarization and neurotransmitter (e.g., ATP, se- medical therapies [27] . Taste is also lost in patients receiv- rotonin) release [22] . The signal is then carried to the ing radiotherapy (head and neck areas). Loss of taste sen- brain by depolarized primary afferent taste neurons. The sitivity is associated with unintentional weight loss and brain represents taste from unique patterns of activity reduced quality of life [28, 29] . Taste and flavor enhance- across large networks of neurons, connecting opercular, ment have been successfully employed as a means of in- insular, and orbito-frontal cortices, among other regions creasing food intake and improving health status in el- [20] . derly patients [30] . Sweet taste is a particularly important topic with re- gards to human health. Our innate attraction to sweet- T1Rs Guide Food Selection tasting foods, which served our ancestors in the tropical Taste is a highly adaptive chemical sense. We use forests, has since become a public health concern. Car- our sense of taste when foraging to identify the chemi- bohydrate-rich foods are no longer scarce, thanks to ad- cal makeup of a potential food source in order to assess vances in agriculture and technology. The amount of its nutrient content. Appetitive taste stimuli reinforce food energy available per capita has increased to the the consumption of needed nutrients. Aversive stimuli, point that the major nutritional challenge for humans of on the other hand, discour- industrialized nations has age the consumption of po- shifted from undernutrition tential toxins or harmful mi- The recent discovery of taste to overnutrition [31] . The crobes. receptors in metabolically active prevalence of conditions re- Umami taste guides the tissues has generated intense interest lated to overnutrition such as consumption of foods rich in in the potential health impacts of HPS obesity, type 2 diabetes mel- free amino acids, which are litus, and fatty liver disease essential for survival. Mono- increased dramatically in the sodium glutamate, a primary elicitor of umami taste, en- latter half of the 20th century [32] . The epidemic of nu- hances the palatability of foods [23] . Umami taste is hy- trition-related diseases has been attributed to a long list pothesized to have evolved to guide the ingestion of of factors, but one of the most often cited causes is the foods rich in free amino acids, including certain vegeta- overconsumption of added-sugar foods, including sug- bles and meats, as well as fermented, aged, or cooked ar-sweetened beverages [33] . High-potency sweeteners foods [24] . Similarly, salty tastes identify sodium and (HPS), which bind and activate T1Rs to stimulate sweet other ions which serve a host of physiological functions, taste, present a low- or no-calorie alternative to sugar including the maintenance of membrane potentials and consumption. Although some observational studies have regulation of blood volume.