Genetics of sweet taste preferences

Abstract

Sweet taste is a powerful factor influencing food acceptance. There is considerable variation in sweet taste perception and preferences within and among species. Although learning and homeostatic mechanisms contribute to this variation in sweet taste, much of it is genetically determined. Recent studies have shown that variation in the T1R genes contributes to within- and between-species differences in sweet taste. In addition, our ongoing studies using the mouse model demonstrate that a significant portion of variation in sweetener preferences depends on genes that are not involved in peripheral taste processing. These genes are likely involved in central mechanisms of sweet taste processing, reward and/or motivation. Genetic variation in sweet taste not only influences food choice and intake, but is also associated with proclivity to drink alcohol. Both peripheral and central mechanisms of sweet taste underlie correlation between sweet-liking and alcohol consumption in animal models and humans. All these data illustrate complex genetics of sweet taste preferences and its impact on human nutrition and health. Identification of genes responsible for within- and between-species variation in sweet taste can provide tools to better control food acceptance in humans and other animals.

Figure 1

Structures of the cat Tas1r2 and human TAS1R2 genes. The cat Tas1r2 gene has a 247-base pair micro-deletion (♠) in exon 3 and stop codons (*) in exons 4 and 6. The exons are shown as black bars; exon numbers and size (bp; shown in parentheses) are indicated above the bars. The % similarity between corresponding human and cat exons at the nucleotide level are indicated under the human exons. Introns are not scaled proportionally because of their large size. Reproduced from Li et al.^[56] with open-access licence from the Public Library of Science (PLoS)

Figure 2

Sequence variants predicted to influence interaction of the T1R2+3 receptor with aspartame. Top panel: VFT domain of the hT1R2 (active–close)-hT1R3 (active–open) heterodimer. The C-alpha trace for hT1R2 is shown as blue ribbon; hT1R3 is shown in purple. Centres of binding regions are shown as green or black spheres. The green spheres (labelled AC) indicate binding regions at the centres of the VFT domains referred to as active sites. Black spheres (labelled AL) indicate binding regions referred to as allosteric sites. Taster/non-taster variant sites are shown as space-filled representation. The hT1R2 segment P348–R352 (PPLSR; shown in green ribbon) is a part of the allosteric site. It is deleted in most aspartame non-tasters and is replaced with PMPNE in the mouse. This segment is important for the spatial arrangement of the putative allosteric site (see bottom panel). Bottom panel: Aspartame (carbon atoms are cyan) bound to the allosteric site of hT1R2 is superposed to aspartame (carbon atoms are purple) bound to the allosteric site of mT1R2. Amino acids within 4.5 Å of bound aspartame in hT1R2 are shown in stick representation (the equivalent amino acids in mT1R2 are shown as shadows). R352 (a part of a polymorphic segment P348–R352) in hT1R2 is predicted to be directly involved in binding of aspartame to the putative allosteric site. Substitution of R352 in hT1R2 with a corresponding residue, E356, in mT1R2 changes orientation of aspartame within the allosteric site and leads to stronger binding of aspartame to the mouse site compared with the human site. This likely interferes with aspartame binding to the active site of mT1R2+3 and prevents receptor activation. Reproduced from Li et al.^[78] by permission of the Oxford University Press

Figure 3

The variation in sweet-liking in humans: individual hedonic ratings of sucrose. ‘Dislikers’ report a general decrease in pleasantness as concentration increases, ‘likers’ report an increase in pleasantness with increasing concentration, and ‘neutrals’ have a minimal affective response to all concentrations of sucrose. Reproduced from Looy and Weingarten^[86] by permission of the Oxford University Press