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Title: CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme based on the Mediterranean diet

Author
item GARAULET, MARTA - Universidad De Murcia
item CORBALAN, M. DOLORES - Universidad De Murcia
item MADRID, JUAN ANTONIO - Universidad De Murcia
item MORALES, ELISA - Universidad De Murcia
item BARAZA, JUAN - Universidad De Murcia
item LEE, YU-CHI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: International Journal of Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/2/2009
Publication Date: 3/1/2010
Citation: Garaulet, M., Corbalan, M., Madrid, J., Morales, E., Baraza, J.C., Lee, Y., Ordovas, J.M. 2010. CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme based on the Mediterranean diet. International Journal of Obesity. 34(3):516-523.

Interpretive Summary: Obesity has been identified “one of today’s most blatantly visible – yet most neglected – public health problems.” This rising epidemic of overweight and obesity has been called by some as “globesity” to clearly reflect that is a global problem and that, unless action is taken, billions will suffer from debilitating conditions associated with this disorder. Overeating and sedentary lifestyle are major environmental factors determining the current globesity; however, genetic factors are also important to predispose some people to obesity. Moreover, genetic factors may also affect the circadian rhythmicity of our daily lives. Nowadays, a clear connection has been established between alterations of the biorhythms (i.e., sleeping) and a number of metabolic diseases including obesity. We have examined the CLOCK gene, a major determinant of our biological master clock in relation to obesity and the ability of obese subjects to lose weight in response to a long term dietary program based on a Mediterranean diet. The presence in these subjects of certain forms of the CLOCK gene was associated with obesity. Moreover, one of those forms was associated with less successful weight loss following a dietary and behavioral intervention program. Therefore, our data support a relationship between CLOCK gene polymorphisms and obesity. Moreover, this gene may be used to predict the outcome of body weight reduction strategies based on low-energy diets.

Technical Abstract: Introduction: The success of obesity therapy is dependent on the genetic background of the patient. Circadian Locomotor Output Cycles Kaput (CLOCK), one of the transcription factors from the positive limb of the molecular clock, is involved in metabolic alterations. Objective: To investigate whether five candidate polymorphisms from CLOCK were associated with anthropometric, metabolic measures and weight loss in response to a behavioral weight reduction programme based on the Mediterranean diet. Methods: Five hundred overweight/obese subjects, aged 20–65 years, who attended outpatient clinics specializing in obesity, were studied. Anthropometric, biochemical and dietary intake variables were analyzed. Effectiveness of the programme and weight loss progression during 28 weeks of treatment was assessed. Results: Four of five CLOCK SNPs selected were significantly associated with obesity variables (Po0.05). The genetic variation in the rs1801260 CLOCK was associated with obesity at baseline and also affected weight loss. Patients with the variant allele (G) lost significantly less weight i(P¼0.008) compared with wild type. Repeated measures analysis showed that weight loss over time was significantly different between rs1801260 CLOCK variations (P¼0.038). Carriers of the G allele displayed greater difficulty in losing weight than non-carriers. In this particular polymorphism, the frequency of short-time sleepers (p6 h per day) was greater in minor allele carriers than in non-carriers (59% vs 41%; Po0.05). CLOCK polymorphisms were also associated with significant differences in total plasma cholesterol at the completion of dietary treatment (Po0.05). Conclusions: We have replicated previous studies showing a relationship between CLOCK gene polymorphisms and obesity. CLOCK rs1801260 SNP may predict the outcome of body weight reduction strategies based on low-energy diets.