SIRT1 and CLOCK 3111T> C combined genotype is associated with evening preference and weight loss resistance in a behavioral therapy treatment for obesity

Abstract

Background: A new negative feedback loop has been proposed, which suggests connections between the circadian clock and SIRTUIN1 (SIRT1)-dependent functions associated with cell survival, development and metabolism.

Objective: To develop a SIRT1 and circadian locomotor output cycles kaput (CLOCK) combined genotype and to assess its associations with the chronotype of subjects and their potential resistance to weight loss in a behavioral treatment for obesity based on a Mediterranean diet.

Design: Overweight /obese subjects (n=1465), aged 20-65 years, who attended outpatient obesity clinics, were genotyped for SIRT1 (rs1467568) and CLOCK (3111T>C, rs1801260). Anthropometric, biochemical and dietary-intake variables were analyzed. Effectiveness of the program and weight loss progression during 30 weeks of treatment was assessed.

Results: We found highly consistent associations between the morning/evening questionnaires across the different genotype categories. Subjects carrying minor alleles at SIRT1 and CLOCK loci (R group) displayed a higher resistance to weight loss and a lower weekly weight loss rate as compared with homozygotes for both major alleles (P group). Significant differences were found across genotypes in weight loss progression during the 30 weeks of treatment (P=0.039). Dietary habits indicated that R carriers had a lower intake of total carbohydrates and monounsaturated fats, and a higher intake of saturated fats than those carrying the intermediate (M) and the P genotype (P=0.02). Plasma ghrelin concentrations were also significantly higher in subjects carrying the R genotype.

Conclusion: Variants of both SIRT1 and CLOCK have an additive effect on resistance to weight loss that could be related to the chronotype of the subject, higher plasma levels of ghrelin and less adherence to Mediterranean diet patterns.

Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Figures

Figure 1

Differences in total weight loss (a) and weight loss rate (g per week) (b) across SIRT1-CLOCK combined genotypes in the total treatment. Data are presented as mean ± s.e.m. based on analysis of variance (ANOVA) and after adjusting for sex, age and study center. R for subjects resistant in total weight loss and weight loss rate (kg), M for intermediate and P for protected subjects. We used different letters to indicate the differences between the groups (P<0.050).

Figure 2

Weight loss progression during 30 weeks of treatment in subjects of different SIRT1-CLOCK combined genotypes (R, M and P) after adjusting for sex, age and study center. R for subjects resistant in total weight loss (kg), M for intermediate and P for protected subjects. Differences between the groups (P<0.050).