A circadian rhythm-related MTNR1B genetic variant (rs10830963) modulate body weight change and insulin resistance after 9 months of a high protein/low carbohydrate vs a standard hypocaloric diet

Abstract

Background & aims: The 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.

Methods: 270 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.

Results: All 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.

Conclusions: our 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.

Keywords: High protein diet; MTNR1B; Standard diet; rs10830963.