PPARγ Pro12Ala interacts with fat intake for obesity and weight loss in a behavioural treatment based on the Mediterranean diet

Mol Nutr Food Res. 2011 Dec;55(12):1771-9. doi: 10.1002/mnfr.201100437. Epub 2011 Nov 21.


Scope: The goal of this study was to examine whether the Pro12Ala polymorphism of peroxisome proliferator-activated receptor γ (PPARγ) is associated with insulin resistance, obesity and weight loss and to analyze potential interactions between fat intake and PPARγ polymorphism in a Spanish overweight/obese population.

Materials and methods: We recruited 1465 subjects enrolled in a behavioural treatment program for obesity based on a Mediterranean diet, which included the following: dietary treatment, physical activity, nutritional education and behavioral techniques. A significant association was found between PPARγ2 Pro12Ala genotype and plasma insulin concentration and homeostasis model assessment insulin resistance. Subjects with the Ala12 genotype had lower insulin levels than those with the Pro12Pro genotype. We detected a gene-diet interaction between the PPARγ Pro12Ala polymorphism and MUFA for BMI and body fat. Furthermore, we detected an interaction between the PPARγ Pro12Ala polymorphism and fat intake for total weight loss (p<0.001). When total fat intake was high, Ala12-carriers exhibited a significantly lower percentage of total weight loss than major-allele-carriers (p=0.037).

Conclusion: Data are consistent with previous results showing a protective role for the Ala12 allele against insulin resistance, and replicate an earlier study that detected an interaction between dietary MUFA and PPARγ2 for BMI. Our detection of a gene-diet interaction between PPARγ Pro12Ala and fat intake for weight loss may explain previous discrepancies among different studies.

Publication types

  • 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

  • Adipose Tissue / metabolism
  • Adult
  • Aged
  • Alleles
  • Anthropometry
  • Body Mass Index
  • Diet, Mediterranean*
  • Dietary Fats / administration & dosage*
  • Fatty Acids, Monounsaturated / administration & dosage
  • Feeding Behavior*
  • Female
  • Genetic Loci
  • Genotype
  • Homeostasis
  • Humans
  • Insulin / blood
  • Insulin Resistance / genetics
  • Interviews as Topic
  • Logistic Models
  • Male
  • Middle Aged
  • Obesity / diet therapy
  • Obesity / genetics*
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • Phenotype
  • Polymorphism, Genetic
  • Spain
  • Weight Loss / drug effects
  • Weight Loss / genetics*
  • Young Adult


  • Dietary Fats
  • Fatty Acids, Monounsaturated
  • Insulin
  • PPAR gamma