ACYL-CoA synthetase long-chain 5 polymorphism is associated with weight loss and metabolic changes in response to a partial meal-replacement hypocaloric diet

Aims:to analyze the effects of the rs2419621 genetic variant of the ACSL5 gene on weight change and metabolic parameters after a partial meal-replacement hypocaloric diet. Methods: this was a non-randomized, single-treatment study with a formula-diet in 44 obese subjects with body mass index (BMI) greater than 35 kg/m2. Patients received nutritional education and a modified diet with two intakes of a normocaloric hyperproteic formula during 3 months. Anthropometric parameters and biochemical profile were measured at baseline and after 3 months. The rs2419621 variant of the ACSL5 gene was assessed using real-time polymerase chain reaction. Results: T-allele carriers showed greater improvement in body weight (CC vs. CT + TT; -7.4 ± 2.1 kg vs. -9.3 ± 1.8 kg; p = 0.01), body mass index (-3.1 ± 0.4 kg/m2 vs. -3.4 ± 0.5 kg/m2; p = 0.02), fat mass (-5.2 ± 1.4 kg vs. -6.4 ± 1.2 kg; p = 0.01) and waist circumference (-6.1 ± 1.1 cm vs. -8.6 ± 0.8 cm; p = 0.02) than non-T-allele carriers. Only subjects with the T allele showed significant improvement in triglyceride levels (-4.6 ± 2.4 md/dL vs. -14.4 ± 2.3 mg/dL; p = 0.01). Finally, improvements in insulin (-2.0 ± 0.3 mU/L vs. -4.5 ± 0.5 mU/L; p = 0.01) and HOMA-IR (-0.4 ± 0.2 units vs. -1.3 ± 0.3 units; p = 0.02) were higher in T-allele carriers than in non-T-allele carriers. Conclusions: our data suggest that the genetic variant (rs2419621) of the ACSL5 gene is associated with diet response after a partial-meal replacement intervention, with greater improvements in adiposity and biochemical parameters in subjects with the T allele.