A circadian rhythm-related MTNR1B genetic variant modulates the effect of weight-loss diets on changes in adiposity and body composition: the POUNDS Lost trial

Abstract

Purpose: A common variant of the melatonin receptor 1B (MTNR1B) gene has been related to increased signaling of melatonin, a hormone previously associated with body fatness mainly through effects on energy metabolism. We examined whether the MTNR1B variant affects changes of body fatness and composition in response to a dietary weight loss intervention.

Methods: The MTNR1B rs10830963 variant was genotyped for 722 overweight and obese individuals, who were randomly assigned to one of four diets varying in macronutrient composition. Anthropometric and body composition measurements (DXA scan) were collected at baseline and at 6 and 24 months of follow-up.

Results: Statistically significant interactions were observed between the MTNR1B genotype and low-/high-fat diet on changes in weight, body mass index (BMI), waist circumference (WC) and total body fat (p interaction = 0.01, 0.02, 0.002 and 0.04, respectively), at 6 months of dietary intervention. In the low-fat diet group, increasing number of the sleep disruption-related G allele was significantly associated with a decrease in weight (p = 0.004), BMI (p = 0.005) and WC (p = 0.001). In the high-fat diet group, carrying the G allele was positively associated with changes in body fat (p = 0.03). At 2 years, the associations remained statistically significant for changes in body weight (p = 0.02), BMI (p = 0.02) and WC (p = 0.048) in the low-fat diet group, although the gene-diet interaction became less significant.

Conclusions: The results suggest that carriers of the G allele of the MTNR1B rs10830963 may have a greater improvement in body adiposity and fat distribution when eating a low-fat diet.

Keywords: Adiposity; Gene–diet interaction; High-fat diet; Melatonin receptor 1B; Weight-loss intervention.

Figure 1

Effect of the MTNR1B rs10830963 genetic variant and fat diets on changes in body weight (A), BMI (B), WC (C) and body fat mass (D) at 6 months of diet intervention (black bars, CC genotype; gray bars, CG genotype, white bars, GG genotype). Data are means (SD) after adjusted for age, sex, ethnicity, BMI at the baseline (if appropriate) and value for the respective outcome trait at baseline

Figure 2

Effect of the MTNR1B rs10830963 genetic variant and fat diets on changes in body weight (A), BMI (B), WC (C) and body fat mass (D) at 6 months and 2 years of diet intervention (black circle and solid line, CC genotype; gray circle and gray solid line, CG genotype; white circle and dotted line, GG genotype). Data are means (SE) after adjusted for age, sex, ethnicity, BMI at baseline (if appropriate) and the value for the respective outcome trait at baseline