Detection of Sweet and Umami Taste in the Absence of Taste Receptor T1r3

Damak, Sami; Rong, Minqing; Yasumatsu, Keiko; Kokrashvili, Zaza; Varadarajan, Vijaya; Zou, Shiying; Jiang, Peihua; Ninomiya, Yuzo; Margolskee, Robert F.

doi:10.1126/science.1087155

Cited by 548 publications

(570 citation statements)

References 18 publications

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“…Standard histology techniques were used on paraffin sections of tissues fixed with the Davidson's fixative; immunohistochemistry was as previously described (6,56,57). Epididymal sperm count and sperm evaluation was as described in ref.…”

Section: Methodsmentioning

confidence: 99%

Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility

Mosinger

Redding

Parker

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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TAS1R taste receptors and their associated heterotrimeric G protein gustducin are involved in sugar and amino acid sensing in taste cells and in the gastrointestinal tract. They are also strongly expressed in testis and sperm, but their functions in these tissues were previously unknown. Using mouse models, we show that the genetic absence of both TAS1R3, a component of sweet and amino acid taste receptors, and the gustducin α-subunit GNAT3 leads to malespecific sterility. To gain further insight into this effect, we generated a mouse model that expressed a humanized form of TAS1R3 susceptible to inhibition by the antilipid medication clofibrate. Sperm formation in animals without functional TAS1R3 and GNAT3 is compromised, with malformed and immotile sperm. Furthermore, clofibrate inhibition of humanized TAS1R3 in the genetic background of Tas1r3 −/− , Gnat3 −/− doubly null mice led to inducible male sterility. These results indicate a crucial role for these extraoral "taste" molecules in sperm development and maturation. We previously reported that blocking of human TAS1R3, but not mouse TAS1R3, can be achieved by common medications or chemicals in the environment. We hypothesize that even low levels of these compounds can lower sperm count and negatively affect human male fertility, which common mouse toxicology assays would not reveal. Conversely, we speculate that TAS1R3 and GNAT3 activators may help infertile men, particularly those that are affected by some of the mentioned inhibitors and/or are diagnosed with idiopathic infertility involving signaling pathway of these receptors.phenoxy compounds | spermiogenesis

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Section: Methodsmentioning

confidence: 99%

Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility

Mosinger

Redding

Parker

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Knockout of each subunit abolishes preference for non-nutritive sweeteners and sugar in brief taste tests [67,68]. However, in T1r3 knockout mice, prolonged experience with sugar allows a preference to develop, presumably due to rewarding post-ingestive effects [65,68].…”

Section: Genetic Modelsmentioning

confidence: 99%

The role of dopamine in the pursuit of nutritional value

McCutcheon

2015

Physiology & Behavior

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Acquiring enough food to meet energy expenditure is fundamental for all organisms. Thus, mechanisms have evolved to allow foods with high nutritional value to be readily detected, consumed, and remembered. Although taste is often involved in these processes, there is a wealth of evidence supporting the existence of taste-independent nutrient sensing. In particular, post-ingestive mechanisms arising from the arrival of nutrients in the gut are able to drive food intake and behavioural conditioning. The physiological mechanisms underlying these effects are complex but are believed to converge on mesolimbic dopamine signalling to translate post-ingestive sensing of nutrients into reward and reinforcement value. Discerning the role of nutrition is often difficult because food stimulates sensory systems and post-ingestive pathways in concert. Thus, in this mini-review, I discuss the various methods that may be used to study post-ingestive processes in isolation including sham-feeding, nonnutritive sweeteners, post-ingestive infusions, and pharmacological and genetic methods. Using this structure, I present the evidence that dopamine is sensitive to nutritional value of certain foods and examine how this affects learning about food, the role of taste, and the implications for human obesity.

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“…This finding could be explained by non-T1R3 mediated sweet taste (Damak et al 2003). K ATP channels are part of a metabolic signaling pathway and are expressed in many taste cells and may contribute to depolarization of these cells and activation of downstream signaling events (Merigo et al 2011;Yee et al 2011).…”

Section: Discussionmentioning

confidence: 99%

“…K ATP channels are part of a metabolic signaling pathway and are expressed in many taste cells and may contribute to depolarization of these cells and activation of downstream signaling events (Merigo et al 2011;Yee et al 2011). In T1R3 knockout mice, nerve responses to glucose were diminished but not abolished (Damak et al 2003), indicating residual signaling from sugars in mice.…”

Section: Discussionmentioning

confidence: 99%

Lipid-Lowering Pharmaceutical Clofibrate Inhibits Human Sweet Taste

Kochem

Breslin

2016

CHEMSE

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T1R2-T1R3 is a heteromeric receptor that binds sugars, high potency sweeteners, and sweet taste blockers. In rodents, T1R2-T1R3 is largely responsible for transducing sweet taste perception. T1R2-T1R3 is also expressed in non-taste tissues, and a growing body of evidence suggests that it helps regulate glucose and lipid metabolism. It was previously shown that clofibric acid, a blood lipid-lowering drug, binds T1R2-T1R3 and inhibits its activity in vitro. The purpose of this study was to determine whether clofibric acid inhibits sweetness perception in humans and is, therefore, a T1R2-T1R3 antagonist in vivo. Fourteen participants rated the sweetness intensity of 4 sweeteners (sucrose, sucralose, Na cyclamate, acesulfame K) across a broad range of concentrations. Each sweetener was prepared in solution neat and in mixture with either clofibric acid or lactisole. Clofibric acid inhibited sweetness of every sweetener. Consistent with competitive binding, inhibition by clofibric acid was diminished with increasing sweetener concentration. This study provides in vivo evidence that the lipid-lowering drug clofibric acid inhibits sweetness perception and is, therefore, a T1R carbohydrate receptor inhibitor. Our results are consistent with previous in vitro findings. Given that T1R2-T1R3 may in part regulate glucose and lipid metabolism, future studies should investigate the metabolic effects of T1R inhibition.

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Detection of Sweet and Umami Taste in the Absence of Taste Receptor T1r3

Cited by 548 publications

References 18 publications

Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility

Genetic loss or pharmacological blockade of testes-expressed taste genes causes male sterility

The role of dopamine in the pursuit of nutritional value

Lipid-Lowering Pharmaceutical Clofibrate Inhibits Human Sweet Taste

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