Effects of C358A polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) on weight loss, adipocytokines levels, and insulin resistance after a high polyunsaturated fat diet in obese patients.

ABSTRACT

BACKGROUND AND AIMS: The C385A polymorphism of FAAH gene (rs324420C>A) has been associated with obesity. We investigate the role of this polymorphism on anthropometric and insulin resistance responses to a high polyunsaturated fat hypocaloric diet. METHODS: Obese individuals (no.=99) were assessed at baseline and after 3 months of a high polyunsaturated fat hypocaloric diet. RESULTS: Seventy-one patients (71.7%) had the genotype C385C and 28 (28.3%) patients had the C385A (26 patients, 26.3%) or A358A (2 patients, 2.0%) (A allele carriers group) genotype. In A allele carriers and after dietary intervention, total cholesterol (-16.3 ± 37.4 mg/dl) and LDL-cholesterol (-12.9 ± 6.5 mg/dl) levels decreased. In subjects with C385C genotype, the decreases were significant in total cholesterol (-12.3 ± 27.4 mg/dl), LDL-cholesterol (-7.5 ± 20.5 mg/dl), insulin (-2.2 ± 6.2 mUI/l), and homeostasis model assessment of insulin resistance (HOMA-R) (-0.79 ± 1.15 units) levels. The weight loss was similar in both genotype groups (-4.1 ± 3.8 kg vs -4.2 ± 3.2 kg). Only leptin levels had a significant similar decrease in both genotypes. CONCLUSION: Subjects with C385C genotype of the FAAH showed an improvement on insulin and HOMA-R levels with a high polyunsaturated fat hypocaloric diet after weight loss during 3 months.