Background: The role of ADIPOQ gene variants in weight loss after different dietary fat amounts remains unclear. Objective: Our aim was to analyze the effects of ADIPOQ gene polymorphism rs266729 on metabolic changes after two different amounts of dietary fat in two hypocaloric diets. Design: A population of 283 obese patients was recruited in a randomized clinical trial with two diets: Diet HF (high-fat diet: 38% carbohydrates, 24% proteins, and 38% fats) versus Diet LF (low-fat diet: 53% carbohydrates, 20% proteins, and 27% fats). Before and after 3 months, an anthropometric evaluation, an assessment of nutritional intake, and a biochemical analysis were carried out. The variant of the ADIPOQ gene was assessed by real-time PCR. Results: Weight loss was similar with both diets in both genotypes (CC vs. CG+GG). After dietary intervention with Diet HF, only subjects with CC genotype showed a significant improvement in insulin levels (–3.3 ± 0.6 vs. –1.8 ± 0.9 mU/L; p = 0.03) and the homeostasis model assessment for insulin resistance (HOMA-IR) (–1.3 ± 0.1 vs. –0.8 ± 0.2 units; p = 0.02). After Diet LF, subjects with CC genotype showed a significant improvement in total cholesterol levels (CC vs. CG+GG) (–15.3 ± 1.4 vs. –6.4 ± 1.3 mg/dL; p = 0.01), LDL cholesterol (–14.6 ± 1.8 vs. –6.4 ± 1.3 mg/dL; p = 0.01), insulin levels (–4.6 ± 1.0 vs. –1.6 ± 0.5 mU/L; p = 0.01), and HOMA-IR (–1.6 ± 0.1 vs. –1.0 ± 0.2 units; p = 0.02). Only subjects with CC genotype showed a significant increase of adiponectin levels after both diets (CC vs. CG+GG): Diet HF (10.6 ± 2.0 vs. 1.8 ± 1.0 ng/dL; p = 0.01) and Diet LF (16.1 ± 2.8 vs. 1.3 ± 1.0 ng/dL: p = 0.03). Conclusion: CC genotype of ADIPOQ gene variantrs266729 was associated with a better metabolic response after both diets. Additionally, Diet LF produced a significant improvement in lipid profile in noncarriers of allele G.

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