Abstract

Objective: A common "obesity-risk" variant rs9939609 in the FTO gene was recently found to affect appetite, and the gene is sensitive to regulation of amino acids. We examined the interaction between FTO genotype and protein intake on the long-term changes in appetite in a randomized controlled trial. Research Design and Methods: We genotyped FTO rs9939609 in 737 overweight adults in the 2-year Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) trial and assessed four appetite related traits including cravings, fullness, hunger, and prospective consumption. Results: We found that dietary protein significantly modified genetic effects on changes in food cravings at 6 months, after adjustment for age, sex, ethnicity, baseline body mass index, weight change, baseline value for food cravings (P for interaction=0.027). The A allele was associated with a greater decrease in food cravings among the participants with high protein diet intake (P=0.027), but not in those low protein diet group (P= 0.384). Weight regain from 6 months to 24 months attenuated the gene-protein interactions. Protein intakes did not modify the FTO genotype effects on other appetite measures. Conclusions: Our data suggest that individuals with the FTO rs9939609 A allele might obtain more benefits in reduction of food cravings by choosing a hypocaloric and higher protein weight-loss diet. Keywords: diet, genetic variation, food cravings, gene-diet interaction, weight-loss trial

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