FTO genotype, dietary protein, and change in appetite: the Preventing Overweight Using Novel Dietary Strategies trial

Abstract

Background: A common obesity-risk variant rs9939609 in the fat mass- and obesity-associated (FTO) gene was recently shown to affect appetite, and the gene is sensitive to the regulation of amino acids.

Objective: We examined the interaction between FTO genotype and protein intake on the long-term changes in appetite in a randomized controlled trial.

Design: We genotyped FTO rs9939609 in 737 overweight adults in the 2-y Preventing Overweight Using Novel Dietary Strategies trial and assessed 4 appetite-related traits including cravings, fullness, hunger, and prospective consumption.

Results: We showed that dietary protein significantly modified genetic effects on changes in food cravings and appetite scores at 6 mo after adjustment for age, sex, ethnicity, baseline body mass index, weight change, and baseline value for respective outcomes (P-interaction = 0.027 and 0.048, respectively). The A allele was associated with a greater decrease in food cravings and appetite scores in participants with high-protein-diet intake (P = 0.027 and 0.047, respectively) but not in subjects in the low-protein-diet group (P = 0.384 and 0.078, respectively). The weight regain from 6 to 24 mo attenuated gene-protein interactions. Protein intakes did not modify FTO genotype effects on other appetite measures.

Conclusion: Our data suggest that individuals with the FTO rs9939609 A allele might obtain more benefits in a reduction of food cravings and appetite by choosing a hypocaloric and higher-protein weight-loss diet. This trial was registered at clinicaltrials.gov as NCT00072995.

Figures

FIGURE 1.

Mean (±SE) effects of the FTO rs9939609 genotype on 6-mo changes in appetite measurements in response to dietary protein. Data were included for 84 (TT), 146 (TA), and 68 (AA) participants in low-protein diet groups and 100 (TT), 154 (TA), and 57 (AA) participants in high-protein diet groups at 6 mo. Data were calculated by using general linear models after adjustment for age, sex, ethnicity, weight change, and baseline values for respective phenotypes. To test for interactions, generalized linear models were used to examine genotype-by-intervention interactions as independent predictors of changes in primary endpoints after adjustment for age, sex, ethnicity, baseline BMI, weight change, and the baseline value for the respective outcome trait. All reported P values were nominal and 2-sided, and P = 0.05 was considered significant. App, appetite.