Abstract
Background Circadian Locomotor Output Cycles Kaput (CLOCK), an essential element of the positive regulatory arm in the human biological clock, is involved in metabolic regulation. The aim was to investigate the behavioral (sleep duration, eating patterns and chronobiological characteristics) and hormonal (plasma ghrelin and leptin concentrations) factors which could explain the previously reported association between the CLOCK 3111T/C SNP and weight loss.Methodology/Principal FindingsWe recruited 1495 overweight/obese subjects (BMI: 25–40 kg/m2) of 20–65 y. who attended outpatient obesity clinics in Murcia, in southeastern Spain. We detected an association between the CLOCK 3111T/C SNP and weight loss, which was particularly evident after 12–14 weeks of treatment (P = 0.038). Specifically, carriers of the minor C allele were more resistant to weight loss than TT individuals (Mean±SEM) (8.71±0.59 kg vs 10.4±0.57 kg) C and TT respectively. In addition, our data show that minor C allele carriers had: 1. shorter sleep duration Mean ± SEM (7.0±0.05 vs 7.3±0.05) C and TT respectively (P = 0.039), 2. higher plasma ghrelin concentrations Mean ± SEM (pg/ml) (1108±49 vs 976±47)(P = 0.034); 3. delayed breakfast time; 4. evening preference and 5. less compliance with a Mediterranean Diet pattern, as compared with TT homozygotes.Conclusions/SignificanceSleep reduction, changes in ghrelin values, alterations of eating behaviors and evening preference that characterized CLOCK 3111C carriers could be affecting weight loss. Our results support the hypothesis that the influence of the CLOCK gene may extend to a broad range of variables linked with human behaviors.
Highlights
The current prevalence of obesity has been attributed to changes in our diet and physical activity; recent research has raised interest in the possibility that changes in our daily behavioral patterns may be a significant contributing factor [1]
We previously demonstrated associations between the Circadian Locomotor Output Cycles Kaput (CLOCK) 3111T/C single nucleotide polymorphism (SNP), baseline body weight and weight reduction in obese patients participating in a Mediterranean diet based weight reduction program [8]
General characteristics General characteristics of the population studied are shown in CLOCK 3111T/C SNP and weight loss We found an association between the CLOCK 3111T/C SNP
Summary
The current prevalence of obesity has been attributed to changes in our diet and physical activity; recent research has raised interest in the possibility that changes in our daily behavioral patterns may be a significant contributing factor [1]. In industrial countries, the amount of daily sleep has declined by 1.5 h over the past century, concurrent with a significant increase in obesity [2] These observed correlations do not support a causal relationship, additional evidence based on data from night-shift workers and sleeprestricted subjects supports the notion that [3] a sleep disruption and modification of the circadian rhythm, may play a significant role in the etiology of obesity. CLOCK disruptions may affect the homeostasis of different metabolic pathways Along these lines, we previously demonstrated associations between the CLOCK 3111T/C (rs1801260) single nucleotide polymorphism (SNP), baseline body weight and weight reduction in obese patients participating in a Mediterranean diet based weight reduction program [8]. The aim was to investigate the behavioral (sleep duration, eating patterns and chronobiological characteristics) and hormonal (plasma ghrelin and leptin concentrations) factors which could explain the previously reported association between the CLOCK 3111T/C SNP and weight loss
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