The 825T allele of the G protein beta3-subunit gene (GNB3) is a thrifty genotype associated with an increased risk for obesity. We aimed to determine whether the 825T allele is modifying the subjective response to extended fasting.
We genotyped 108 subjects who underwent an 8-day modified medical fasting treatment [total energy intake <350 kcal (1465 kJ)/day] for the GNB3 C825T polymorphism. Perceived hunger and mood were recorded daily by self-rating visual analogue scales.
Whereas weight loss was not dependent on genotype, both mood and hunger were significantly associated with genotype, with homozygous CC genotype carriers having best mood (p = 0.004) and least hunger (p = 0.036) during fasting compared to TT genotype carriers.
Pronounced mental discomfort during fasting in 825T allele carriers might partly explain their increased risk for obesity. The strong association between the subjective response to fasting with GNB3 genotypes indicates a role of the gene in the behavioural regulation of food intake, which should be further considered in nutritional intervention studies.