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

Feb 8, 2012International journal of obesity (2005)

Combined SIRT1 and CLOCK gene variants are linked to evening activity and difficulty losing weight during behavioral obesity treatment

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Abstract

Subjects with specific genetic variants showed a higher resistance to weight loss during a 30-week obesity treatment.

Overweight and obese individuals (n=1465) were genotyped for SIRT1 and CLOCK variants.
Carriers of minor alleles at SIRT1 and CLOCK displayed a lower weekly weight loss rate compared to those with major alleles.
Significant differences in weight loss progression were observed across genotype categories (P=0.039).
Dietary habits indicated that R genotype carriers had lower carbohydrate and monounsaturated fat intake, but higher saturated fat intake.
Plasma ghrelin levels were significantly elevated in subjects with the R genotype.

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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.

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

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