Influence of different CLA isomers on insulin resistance, body weight and adipozytokines is dependent on PPARγ2 Pro12Ala polymorphism

Conjugated linoleic acids (CLAs) showed anti-obesity and anti-diabetic effects in certain animal models. However, evidence in humans is currently conflicting. This could partly be explained by isomer-specific properties of CLA, the different dosages of CLA studied and the genetic background of individuals. In several studies the rare Ala-allele in the peroxysome proliferator-activated receptor γ2 (PPARγ2) gene has been associated with a reduced risk for type 2 diabetes but paradoxically weight gain. CLAs are natural PPARγ ligands. We examined in a human trial effects of different isomers of supplemental CLA compared to the effects of linoleic oil in subjects with PPARγ2 Pro12Ala polymorphisms on fasting and postprandial metabolic parameters and adipocytokines. 35 middle-aged men underwent four intervention periods in a cross-over study design, four weeks each, in randomized order: BMI-matched subjects with both genotypes received either 3.4g cis-9-, trans-11 CLA or t10c12 CLA or a commercially available 1:1 mix of both isomers or reference oil (linoleic acid (LA) from safflower oil). Adipocytokines (leptin, adiponectin), insulin, glucose and triglycerides in the fasting state and after a standardized mixed meal were assessed before and at the end of each intervention period. In the Ala12Ala-group trans-10,cis-12 CLA caused isomer-specific weight gain (p=0.03), tended to increase postprandial insulin levels (p=0.05) and insulin resistance (p=0.07). The isomer mix and c9t10 CLA tended to improved insulin resistance (p=0.05), which was not explained by adiponectin (p=0.09). In Pro12Pro-group t10c12 CLA resulted in a significant reduction of waist circumference (p=0.03) and a tendency to lower leptin values in both, the fasting state (p=0.08) and postprandial (p=0.06). In summary, individual CLA-isomers have different effects on metabolism in Ala-and Pro- carriers. CLA-isomer c9t10 and the commercial CLA-mix seem to have beneficial effects on insulin sensitivity compared to LA, while t10c12 CLA adversely affects body weight and insulin sensitivity in the rare PPAR-genotype.