The aim of the present study was to investigate the association of PLIN1 11482G>A (rs894160) and PLIN1 13041A>G (rs2304795) polymorphisms with body composition, energy and substrate metabolism, and the metabolic response to a 12-week energy-restricted diet in obese women. The study comprised a total of seventy-eight obese (BMI 34·0 (SD 2·8) kg/m(2)) women (age 36·7 (SD 7) years). We measured weight, height and waist circumference before and after a 12-week controlled energy-restricted diet intervention. Body fat mass and lean mass were measured by dual-energy X-ray absorptiometry. RMR and lipid oxidation rate were measured by indirect calorimetry. We also analysed fasting plasma glucose, insulin, cholesterol and leptin. Women carrying the 11482A allele had a lower reduction in waist circumference than non-A allele carriers (3·2 (SD 0·5) v. 4·6 (SD 0·6) %, respectively, P = 0·047; P for gene-diet interaction = 0·064). Moreover, women with the 11482A allele had a higher decrease in lipid oxidation rate than non-A allele carriers (58·9 (SD 6·7) v. 31·3 (SD 8·2) %, respectively, P = 0·012; P for gene-diet interaction = 0·004). There was no interaction effect between the 13041A>G polymorphism and diet-induced changes on the outcome variables (all P>0·1). These results confirm and extend previous findings suggesting that the PLIN1 11482G>A polymorphism plays a modulating role on diet-induced changes in body fat and energy metabolism in obese women.