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Review
. 2016 Jul 15;7(4):806S-22S.
doi: 10.3945/an.115.011270. Print 2016 Jul.

Genetics of Amino Acid Taste and Appetite

Alexander A Bachmanov  1 , Natalia P Bosak  2 , John I Glendinning  3 , Masashi Inoue  4 , Xia Li  2 , Satoshi Manita  4 , Stuart A McCaughey  2 , Yuko Murata  5 , Danielle R Reed  2 , Michael G Tordoff  2 , Gary K Beauchamp  6
Affiliations
Review

Genetics of Amino Acid Taste and Appetite

Alexander A Bachmanov et al. Adv Nutr. .

Abstract

The consumption of amino acids by animals is controlled by both oral and postoral mechanisms. We used a genetic approach to investigate these mechanisms. Our studies have shown that inbred mouse strains differ in voluntary amino acid consumption, and these differences depend on sensory and nutritive properties of amino acids. Like humans, mice perceive some amino acids as having a sweet (sucrose-like) taste and others as having an umami (glutamate-like) taste. Mouse strain differences in the consumption of some sweet-tasting amino acids (d-phenylalanine, d-tryptophan, and l-proline) are associated with polymorphisms of a taste receptor, type 1, member 3 gene (Tas1r3), and involve differential peripheral taste responsiveness. Strain differences in the consumption of some other sweet-tasting amino acids (glycine, l-alanine, l-glutamine, and l-threonine) do not depend on Tas1r3 polymorphisms and so must be due to allelic variation in other, as yet unknown, genes involved in sweet taste. Strain differences in the consumption of l-glutamate may depend on postingestive rather than taste mechanisms. Thus, genes and physiologic mechanisms responsible for strain differences in the consumption of each amino acid depend on the nature of its taste and postingestive properties. Overall, mouse strain differences in amino acid taste and appetite have a complex genetic architecture. In addition to the Tas1r3 gene, these differences depend on other genes likely involved in determining the taste and postingestive effects of amino acids. The identification of these genes may lead to the discovery of novel mechanisms that regulate amino acid taste and appetite.

Keywords: behavior; consumption; gustatory nerves; inbred strain; intake; mouse; preference; sweet; umami.

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Conflict of interest statement

Author disclosures: AA Bachmanov, NP Bosak, JI Glendinning, M Inoue, X Li, S Manita, SA McCaughey, Y Murata, DR Reed, MG Tordoff, GK Beauchamp, no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Amino acid solution intakes (top) and preference scores (bottom) of B6 and 129 mice in 48-h 2-bottle choice tests with ascending concentrations of amino acid solutions. Values are means ± SEs, n = 7–18. The dotted horizontal lines show thresholds of preference (75%) and avoidance (25%). *Significant difference between B6 and 129 strains at a given concentration, P < 0.05 (post hoc or planned comparison tests). B6, C57BL/6ByJ inbred mouse strain; BW, body weight; 129, 129P3/J inbred mouse strain. Adapted from references – with permission.
FIGURE 2
FIGURE 2
Chorda tympani nerve responses to lingual stimulation with amino acids (relative to 100 mM NH4Cl) in B6 and 129 mice. Values are means ± SEs, n = 5–7. *Significant difference between B6 and 129 strains at a given concentration, P < 0.05 (t test). B6, C57BL/6ByJ inbred mouse strain; 129, 129P3/J inbred mouse strain. Adapted from references and with permission.
FIGURE 3
FIGURE 3
CTA generalization in B6 and 129 mice conditioned to avoid 100-mM glycine. Lick ratios were calculated by dividing lick numbers of individual conditioned (LiCl-treated) mice by the mean lick rate of the control (NaCl-treated) group. Values are means ± SEs, n = 7–10. *Significant decrease in lick rate in conditioned mice relative to control mice, P < 0.05 (post hoc test). B6, C57BL/6ByJ inbred mouse strain; CTA, conditioned taste aversion; LiCl, lithium chloride; 129, 129P3/J inbred mouse strain. Adapted from reference with permission.
FIGURE 4
FIGURE 4
CTA generalization in B6 and 129 mice conditioned to avoid 100-mM monosodium l-glutamate. Lick ratios were calculated by dividing lick numbers of individual conditioned (LiCl-treated) mice by the mean lick rate of the control (NaCl-treated) group. Values are means ± SEs, n = 6–10. *Significant decrease in lick rate in conditioned mice relative to control mice, P < 0.05 (post hoc test). B6, C57BL/6ByJ inbred mouse strain; CTA, conditioned taste aversion; LiCl, lithium chloride; MSG, monosodium l-glutamate; 129, 129P3/J inbred mouse strain. Adapted from reference with permission.
FIGURE 5
FIGURE 5
Distal chromosome 4 interval mapping of amino acid intakes (in mL/mouse; top) and preference scores (in %; bottom) measured in 96-h 2-bottle choice tests, n = 450–455. The x axis shows distances between chromosomal markers in cM estimated by using MAPMAKER/EXP (http://www.broadinstitute.org/genome_software). Marks on the x axis show marker positions. The arrow indicates the position of the Tas1r3 gene. The curves trace the LOD scores calculated under an unconstrained (free) model by using MAPMAKER/QTL. The dotted horizontal lines show the threshold for significant (LOD: 4.3) linkage. cM, centimorgan; LOD, logarithm of the odds; Tas1r3, taste receptor, type 1, member 3 gene. Adapted from reference with permission.
FIGURE 6
FIGURE 6
Amino acid solution intakes (top) and preference scores (bottom) of F2 mice with different Tas1r3 genotypes in 96-h 2-bottle choice tests. Values are means ± SEs, n = 110–219. The dotted horizontal lines show thresholds of preference (75%) and avoidance (25%). The solid horizontal lines indicate significant differences between genotypes, P < 0.01 (planned comparison test). B6, genotype of the C57BL/6ByJ inbred mouse strain; F2, hybrids of the second filial generation; Tas1r3, taste receptor, type 1, member 3 gene; 129, genotype of the 129P3/J inbred mouse strain. Adapted from reference with permission.
FIGURE 7
FIGURE 7
Distal chromosome 4 interval mapping of chorda tympani responses to oral stimulation with amino acids, n = 42–58. Concentrations are shown next to the corresponding curves, with the exception of 1- to 300-mM glycine with no significant linkages to this chromosomal region. The x axis shows distances between chromosomal markers in cM estimated by using MAPMAKER/EXP. Marks on the x axis show marker positions. The arrows indicate the position of the Tas1r3 gene. The curves trace the LOD scores calculated under an unconstrained (free) model by using MAPMAKER/QTL. The dotted horizontal lines show the threshold for significant (LOD: 4.3) linkage. cM, centimorgan; LOD, logarithm of the odds; Tas1r3, taste receptor, type 1, member 3 gene. Adapted from reference with permission.
FIGURE 8
FIGURE 8
Chorda tympani nerve responses to lingual stimulation with amino acids (relative to 100-mM NH4Cl) in F2 mice with different Tas1r3 genotypes. Values are means ± SEs, n = 13–23. *Significant main effect of genotype at a given concentration, P < 0.01 (1-factor ANOVA). B6, genotype of the C57BL/6ByJ inbred mouse strain; F2, hybrids of the second filial generation; Tas1r3, taste receptor, type 1, member 3 gene; 129, genotype of the 129P3/J inbred mouse strain. Adapted from reference with permission.
FIGURE 9
FIGURE 9
Amino acid solution intakes (top) and preference scores (bottom) of congenic mice with different Tas1r3 genotypes in 48-h 2-bottle choice tests with ascending concentrations of amino acid solutions. Values are means ± SEs, n = 10–14. The dotted horizontal lines show thresholds of preference (75%) and avoidance (25%). *Significant difference between mice with B6/129 and 129/129 Tas1r3 genotypes at a given concentration, P < 0.05 (planned comparison tests). B6, genotype of the C57BL/6ByJ inbred mouse strain; BW, body weight; Tas1r3, taste receptor, type 1, member 3 gene; 129, genotype of the 129P3/J inbred mouse strain. Adapted from reference with permission.
FIGURE 10
FIGURE 10
Initial licking responses to a range of concentrations of amino acid solutions in brief-access tests of congenic mice with different Tas1r3 genotypes. The y axis shows the standardized lick ratios calculated by dividing the mean number of licks taken per trial by the maximum number of licks that the same mouse could potentially take across a 5-s trial. Values are means ± SEs, n = 17–20. *Significant difference between mice with B6/129 and 129/129 Tas1r3 genotypes at a given concentration, P < 0.05 (planned comparison test). B6, genotype of the C57BL/6ByJ inbred mouse strain; Tas1r3, taste receptor, type 1, member 3 gene; 129, genotype of the 129P3/J inbred mouse strain. Adapted from reference with permission.
FIGURE 11
FIGURE 11
Chorda tympani nerve responses to lingual stimulation with amino acids (relative to 100-mM NH4Cl) in congenic mice with different Tas1r3 genotypes. Values are medians ± median absolute deviations, n = 10–14. *Significant difference between mice with B6/129 and 129/129 Tas1r3 genotypes at a given concentration, P < 0.05 (Mann-Whitney U test). B6, genotype of the C57BL/6ByJ inbred mouse strain; Tas1r3, taste receptor, type 1, member 3 gene; 129, genotype of the 129P3/J inbred mouse strain. Adapted from reference with permission.
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