Background & aimsThe risk allele (G) of rs10830963 in the melatonin receptor 1 B (MTNR1B) gene presents an association with biochemical parameters and obesity. We study the effect of this SNP on insulin resistance and weight loss secondary to two hypocaloric diets. Methods270 obese subjects were randomly allocated during 9 months (Diet HP: a high protein/low carbohydrate vs. Diet S: a standard severe hypocaloric diets). Anthropometric parameters, fasting blood glucose, C-reactive protein (CRP), insulin concentration, insulin resistance (HOMA-IR), lipid profile and adipocytokines levels were measured. Genotype of MTNR1B gene polymorphism (rs10830963) was evaluated. ResultsAll adiposity parameters, systolic blood pressure and leptin levels decreased in all subjects after both diets. This improvement of adiposity parameters was higher in non-G allele carriers than G allele carriers. After weight loss with Diet HP, (CC vs. CG + GG at 9 months); total cholesterol (delta: −9.9 ± 2.4 mg/dl vs. −4.8 ± 2.2 mg/dl:p < 0.05), LDL-cholesterol (delta: −8.3 ± 1.9 mg/dl vs. −5.1 ± 2.2 mg/dl: p < 0.05), insulin (delta: −4.7 ± 0.8 UI/L vs. −0.9 ± 1.0 UI/L: p < 0.05), triglycerides (delta: −17.7 ± 3.9 mg/dl vs. −6.1 ± 2.8 mg/dl: p < 0.05) and HOMA IR (delta: −0.8 ± 0.2 units vs. −0.2 ± 0.1 units: p < 0.05) improved only in no G allele carriers. After weight loss with Diet S in non G allele carriers, insulin levels (delta (CC vs. CG + GG): −3.4 ± 0.6 UI/L vs. −1.2 ± 0.4 UI/L: p < 0.05), triglycerides (delta: −29.2 ± 3.4 mg/dl vs. −8.2 ± 3.8 mg/dl: p < 0.05), HOMA-IR (delta (CC vs. CG + GG): −1.1 ± 0.2 units vs. −0.1 ± 0.1 units: p < 0.05), total cholesterol (delta: −15.9 ± 7.4 mg/dl vs. −5.8 ± 2.9 mg/dl:ns) and LDL-cholesterol (delta: −13.7 ± 5.9 mg/dl vs. −6.0 ± 2.9 mg/dl: ns) decreased, too. Conclusionsour study detected a relationship of rs10830963 variant of MTNR1B gene with adiposity changes, cholesterol changes and insulin resistance modification induced by two different hypocaloric during 9 months.