Abstract
In mammals, inter- and intraspecies differences in consumption of sweeteners largely depend on allelic variation of the Tas1r3 gene (locus Sac) encoding the T1R3 protein, a sweet taste receptor subunit. To assess the influence of Tas1r3 polymorphisms on feeding behavior and metabolism, we examined the phenotype of F1 male hybrids obtained from crosses between the following inbred mouse strains: females from 129SvPasCrl (129S2) bearing the recessive Tas1r3 allele and males from either C57BL/6J (B6), carrying the dominant allele, or the Tas1r3-gene knockout strain C57BL/6J-Tas1r3tm1Rfm (B6-Tas1r3-/-). The hybrids 129S2B6F1 and 129S2B6-Tas1r3-/-F1 had identical background genotypes and different sets of Tas1r3 alleles. The effect of Tas1r3 hemizygosity was analyzed by comparing the parental strain B6 (Tas1r3 homozygote) and hemizygous F1 hybrids B6 × B6-Tas1r3-/-. Data showed that, in 129S2B6-Tas1r3-/-F1 hybrids, the reduction of glucose tolerance, along with lower consumption of and lower preference for sweeteners during the initial licking responses, is due to expression of the recessive Tas1r3 allele. Hemizygosity of Tas1r3 did not influence these behavioral and metabolic traits. However, the loss of the functional Tas1r3 allele was associated with a small decline in the long-term intake and preference for sweeteners and reduction of plasma insulin and body, liver, and fat mass.
Highlights
Perception of sweet taste of natural sugars, certain amino acids, and artificial sweeteners acts as a major determinant for strong preference and overconsumption of sweet [1], leading to risks for obesity, type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular complications [2, 3]
In the training sessions of the brief-access licking test (BALT), we found no differences in water intake between 129S2B6F1 and 129S2B6-Tas1r3-/-F1 hybrids
Using the F1 hybrids between C57BL/6J and 129SvPasCrl strains, which had identical background genotypes but carried different Tas1r3 alleles, we demonstrated that the presence of the dominant T allele in 129S2B6F1 hybrids is associated with the stronger preference for sweet solutions compared with 129S2B6Tas1r3-/-F1 mice expressing only the recessive NT allele
Summary
Perception of sweet taste of natural sugars, certain amino acids, and artificial sweeteners acts as a major determinant for strong preference and overconsumption of sweet [1], leading to risks for obesity, type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular complications [2, 3]. Investigations of the last decade suggest an involvement of the sweet taste receptor in the hormonal regulation of metabolism, in addition to its role in sweet taste sensing for detection of calorie-rich products. There is good evidence that the sweet taste receptor proteins, along with several signaltransducing molecules, are expressed in taste buds on the tongue and in organs regulating metabolism [4]. Allelic variation of the Tas1r3 taste receptor gene affects metabolism of glucose
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