Fat and Carbohydrate Intake Modify the Association Between Genetic Variation in the FTO Genotype and Obesity

Am J Clin Nutr. 2009 Nov;90(5):1418-25. doi: 10.3945/ajcn.2009.27958. Epub 2009 Sep 2.


Background: The fat mass and obesity-associated gene (FTO) has been shown to be associated with obesity and to influence appetite regulation.

Objective: The aim was to examine whether dietary factors (macronutrient and fiber intakes) and leisure-time physical activity modify the association between genetic variation in FTO and body mass index (BMI; in kg/m(2)).

Design: A cross-sectional study examined 4839 subjects in the population-based Malmö Diet and Cancer study with dietary data (from a modified diet history method) and information on the genetic variant FTO (rs9939609). Direct anthropometric measures were made, and leisure-time physical activity was determined from the duration participants spent on 18 different physical activities.

Results: Significant interactions between energy-adjusted fat intake and FTO genotype (P = 0.04) and between carbohydrate intake and FTO genotype (P = 0.001) on BMI were observed. The observed increase in BMI across FTO genotypes was restricted to those who reported a high-fat diet, with a mean BMI of 25.3 (95% CI: 24.9, 25.6) among TT carriers and of 26.3 (95% CI: 25.8, 26.8) among AA carriers (P = 0.0001). The FTO variant was not associated with a higher BMI among subjects with lower fat intakes (BMI = 25.7 and 25.9 in TT carriers and AA carriers, respectively; P = 0.42). Among individuals with a low-carbohydrate intake, we observed a mean BMI of 25.4 for TT carriers and of 26.8 for AA carriers. The increase in BMI across genotypes was mainly restricted to individuals who reported low leisure-time physical activity (P for trend = 0.004, P for interaction = 0.05).

Conclusion: Our results indicate that high-fat diets and low physical activity levels may accentuate the susceptibility to obesity by the FTO variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / anatomy & histology
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Appetite / genetics
  • Body Mass Index
  • Body Size
  • Carrier State
  • Cohort Studies
  • Dietary Carbohydrates / pharmacology*
  • Dietary Fats / pharmacology*
  • Energy Intake / genetics*
  • Exercise*
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genotype
  • Humans
  • Leisure Activities
  • Middle Aged
  • Neoplasms / genetics
  • Neoplasms / prevention & control
  • Obesity / epidemiology
  • Obesity / genetics*
  • Proteins / genetics*
  • Reproducibility of Results
  • Surveys and Questionnaires


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