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

Am J Clin Nutr. 2014 May;99(5):1126-30. doi: 10.3945/ajcn.113.082164. Epub 2014 Mar 12.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Alleles
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Appetite / genetics
  • Appetite / physiology*
  • Body Mass Index
  • Diet*
  • Dietary Proteins / administration & dosage*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype*
  • Humans
  • Male
  • Middle Aged
  • Overweight / genetics
  • Overweight / prevention & control*
  • Polymorphism, Single Nucleotide
  • Proteins / genetics*
  • Proteins / metabolism
  • Randomized Controlled Trials as Topic
  • Weight Loss / drug effects
  • Weight Loss / genetics


  • Dietary Proteins
  • Proteins
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human

Associated data

  • ClinicalTrials.gov/NCT00072995