title: Dietary Fat Modifies the Effects of FTO Genotype on Changes in Insulin Sensitivity.
abstract: BACKGROUND
  The common variants in the fat mass and obesity-associated (FTO) gene have been associated with obesity and insulin resistance. Recently, studies also linked FTO variants with macronutrient intakes.
  
  
  OBJECTIVE
  We aimed to investigate whether diet interventions varying in macronutrients modified the effects of FTO genotypes on changes in insulin resistance.
  
  
  METHODS
  We genotyped FTO variants rs1558902 and rs9939609 and measured insulin resistance in fasting plasma samples at baseline and at 6-mo and 2-y visits in 743 overweight or obese adults (aged 30-70 y, 60% women) from a randomized weight-loss dietary interventional trial, the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. We assessed interactions between FTO variants and intakes of dietary fat and protein in relation to change in body weight and insulin resistance using generalized estimating equation models.
  
  
  RESULTS
  We found significant interactions between rs1558902 and dietary fat on changes in homeostasis model assessment of insulin resistance (HOMA-IR) and insulin (P = 0.003 and 0.004, respectively). Each risk allele (A) of rs1558902 showed a trend to be related to a 0.05-unit less reduction in both log(insulin) and log(HOMA-IR) among the participants assigned to low-fat diets (both P = 0.06), but this was not significantly related to reduction in those assigned to high-fat diets (both P > 0.1) during the 2-y period of intervention. Our data showed that the association between rs9939609 and changes in insulin resistance was not modified by diet macronutrient intakes.
  
  
  CONCLUSIONS
  Our results show that carriers of the risk alleles of rs1558902 benefit differently in improving insulin sensitivity by consuming high-fat weight-loss diets rather than low-fat diets. Still, given our data, we acknowledge it is difficult to determine whether fat or carbohydrate contributed to the observed associations.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA;
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA;
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Occupational and Environmental Health and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Pennington Biomedical Research Center of the Louisiana State University System, Baton Rouge, LA; and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rood
authors.affiliation: Pennington Biomedical Research Center of the Louisiana State University System, Baton Rouge, LA; and.
authors.forename: George A
authors.initials: GA
authors.lastname: Bray
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA;
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA nhlqi@channing.harvard.edu.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
mesh_terms: D000328:Adult; D000368:Aged; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D018752:Diet, Fat-Restricted / Q000009:adverse effects; D059305:Diet, High-Fat / Q000009:adverse effects; D004038:Diet, Reducing / Q000379:methods*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism; D050177:Overweight / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D014481:United States; D015431:Weight Loss
chemical_list: D004044:Dietary Proteins; D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
keywords: FTO; diabetes; dietary intervention; gene-diet interaction; insulin resistance