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, food timing, dietary intake, appetite and chronobiologic characteristics) and hormonal (plasma ghrelin and Glucagon-like peptide-1 concentrations) factors that could explain the previously reported association between the CLOCK 3111 T/C SNP and obesity. Methods This cross-sectional study included 403 subjects, overweight and/or obesity, aged 20- 50 years from Iran. The CLOCK rs1801260 data were measured by the PCR–RFLP method. Dietary intake, food timing, sleep duration, appetite and Chrono-type were assessed using validated questionnaires. Ghrelin and GLP-1 were measured by ELIZA in plasma samples. Participants were also divided into three groups based on BMI. Logistic regression models and general linear regression models were used to assess the association between CLOCK genotype and study parameters. Univariate linear regression models were used to assess the interaction between CLOCK and VAS, Food timing, chronotype and sleep on food intakes. Results After controlling for confounding factors, there was a significant difference between genotypes for physical activity (P = 0.001), waist circumference (P˂0.05), BMI (˂0.01), weight (P = 0.001), GLP-1 (P = 0.02), ghrelin (P = 0.04), appetite (P˂0.001), chronotype (P˂0.001), sleep (P˂0.001), food timing (P˂0.001), energy (P˂0.05), carbohydrate (P˂0.05) and fat intake (P˂0.001). Our findings also show that people with the minor allele C who ate lunch after 3 PM and breakfast after 9 AM are more prone to obesity (P˂0.05). furthermore, there was significant interactions between C allele carrier group and high appetite on fat intake (Pinteraction = 0.041), eat lunch after 3 PM on energy intake (Pinteraction = 0.039) and morning type on fat intake (Pinteraction = 0.021). Conclusion Sleep reduction, changes in ghrelin and GLP-1 levels, changes in eating behaviors and evening preference that characterized CLOCK 3111C can all contribute to obesity. Furthermore, the data demonstrate a clear relationship between the timing of food intake and obesity. Our results support the hypothesis that the influence of the CLOCK gene may extend to a wide range of variables related to human behaviors.

Background Recent studies have shown that obesity is largely influenced by heredity and created by the interactions between several genes and environmental and behavioral factors. This study aimed to examine association between variant rs17782313 near melanocortin-4 receptor (MC4R) gene and behavioral and hormonal factors then evaluated interactions between variant MC4R rs17782313 with behavioral and hormonal factors on obesity. Methods This cross-sectional study included 403 subjects, overweight and/or obesity, aged 20–50 years from Iran. The MC4R rs17782313 data were measured by the PCR–RFLP method. Dietary intake, physical activity, stress, anxiety, depression, appetite and emotional eating were assessed by using validated questionnaires. Ghrelin, glucagon-like peptide-1 and cortisol were measured by radioimmunoassay in plasma samples. Participants were also divided into three groups based on rs17782313 genotype and BMI. Results After adjustment for age, gender, energy intake and PA, significant associations were observed between food intake, appetite, emotional eating, stress and physical activity with MC4R rs17782313 (p ˂0.05). Also, significant interactions were observed between fat intake (p-interaction = 0.002), protein intake (p-interaction = 0.01), energy intake (p-interaction = 0.01), emotional eating (p-interaction = 0.02), appetite (p-interaction = 0.04), stress (p-interaction = 0.04), ghrelin (p-interaction = 0.03), cortisol (p-interaction = 0.04) and physical activity (p-interaction = 0.04) and MC4R rs17782313 in terms of BMI. Conclusion Interactions between the CC genotype and high intakes of fat and energy, emotional eating, high appetite, and too much stress with high levels of cortisol and ghrelin probably can have an effect on BMI in overweight/obese subjects.

Background Previous studies have shown that the Circadian locomotor output cycles protein kaput (CLOCK) gene (rs1801260) variant may be associated with obesity risk. Moreover, lifestyle and biochemical parameters have been shown to elicit favorable effects on the obesity risk potentially. Therefore, this study seeks to investigate the effect of lifestyle, biochemical parameters, and CLOCK interaction on food intake and risk of obesity. Methods This cross-sectional study comprised 403 overweight and/or obese subjects aged 20–50 from Iran. The CLOCK rs1801260 data was measured by the PCR-RFLP method. Dietary intake, food timing, sleep duration, appetite, and chronotype were assessed by using validated questionnaires. Ghrelin and Glucagon-like peptide-1 (GLP-1) were measured by radioimmunoassay in plasma samples. Participants were also divided into three groups based on rs1801260 genotype. Univariate linear regression models were used to assess the interaction between CLOCK and study parameters on body weight, and logistic regression models were used for interaction terms between CLOCK and study parameters on food intakes. Results After controlling confounding factors, our findings showed significant interactions between the C-allele carrier group with chronotype (Pinteraction = 0.048), appetite (Pinteraction = 0.035), lunch time (Pinteraction = 0.016), dinner time (Pinteraction = 0.047), GLP-1 (Pinteraction = 0.035), and ghrelin (Pinteraction = 0.022) on obesity. Also, there was a significant interaction between evening type, high appetite, short sleep and late lunch with C-allele on food intake. Conclusion The results of the present study indicate that differences in sleep, appetite hormones, eating behaviors and chronotype influence the risk of obesity differently by CLOCK genotype. These results highlight that diet, gene variants, lifestyle factors, and their interaction should be considered in obesity risk assessment.