Molecular nutrition & food researchNov 22, 2011

PPARγ Pro12Ala gene variant and fat intake linked to obesity and weight loss in Mediterranean diet treatment

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 4, 2026

Abstract

A significant association was found between the Pro12Ala polymorphism of PPARγ and insulin levels in a study of 1,465 overweight and obese individuals.

The Ala12 genotype is associated with lower plasma insulin concentration compared to the Pro12Pro genotype.
A gene-diet interaction was observed between the PPARγ Pro12Ala polymorphism and monounsaturated fatty acids (MUFA) affecting BMI and body fat.
Higher total fat intake resulted in Ala12-carriers having a lower percentage of total weight loss compared to those with the Pro12Pro genotype.
Findings support the protective role of the Ala12 allele against insulin resistance.
The study replicates previous findings regarding dietary interaction and PPARγ2 regarding body weight.

Simplified

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.

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PPARγ Pro12Ala gene variant and fat intake linked to obesity and weight loss in Mediterranean diet treatment

Abstract

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