Ghrelin, Sleep Reduction and Evening Preference: Relationships to CLOCK 3111 T/C SNP and Weight Loss

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.We recruited 1495 overweight/obese subjects (BMI: 25-40 kg/m(2)) 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.Sleep 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

IL-10 released by a new inflammation-regulated lentiviral system efficiently attenuates zymosan-induced arthritis

We thank Dr Filip Lim for critical reading of the manuscript, and Dr S. Bartlett for English editing and helpful discussions. We also thank Drs. David Sancho and M. A. del Pozo for providing us with DCs and immortalized MEFs, respectively. AR is supported by Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I) and Instituto de Salud Carlos III (FIS; PI060122), the Spanish Ministry of Science and Innovation (MICINN;SAF2009-10691) and the Comunidad Autónoma de Madrid (S2006/BIO-0236 and S2010/BMD-2312). JMR is supported by MICINN (RECAVA RD06/0014/005) and by from Fundació La Marató de TV3 (Grant 080731

CLOCK 3111 T/C SNP Interacts with Emotional Eating Behavior for Weight-Loss in a Mediterranean Population

Objective: The goals of this research was (1) to analyze the role of emotional eating behavior on weight-loss progression during a 30-week weight-loss program in 1,272 individuals from a large Mediterranean population and (2) to test for interaction between CLOCK 3111 T/C SNP and emotional eating behavior on the effectiveness of the weight-loss program. Design and Methods: A total of 1,272 overweight and obese participants (BMI: 31±5 kg/m2), aged 20 to 65 years, attending outpatient weight-loss clinics were recruited for this analysis. Emotional eating behavior was assessed by the Emotional Eating Questionnaire (EEQ), a questionnaire validated for overweight and obese Spanish subjects. Anthropometric measures, dietary intake and weight-loss progression were assessed and analyzed throughout the 30-week program. Multivariate analysis and linear regression models were performed to test for gene-environment interaction. Results: Weight-loss progression during the 30-week program differed significantly according to the degree of emotional eating behavior. Participants classified as 'very emotional eaters' experienced more irregular (P = 0.007) weight-loss, with a lower rate of weight decline (−0.002 vs. −0.003, P = 11), lost significantly less weight than those C carriers with a low emotional score (<11) (P = 0.005). Conclusions: Emotional eating behavior associates with weight-loss pattern, progression and total weight-loss. Additionally, CLOCK 3111 T/C SNP interacts with emotional eating behavior to modulate total weight loss. These results suggest that the assessment of this locus and emotional eating behavior could improve the development of effective, long-tern weight-management interventions

Validation of a questionnaire on emotional eating for use in cases of obesity : the Emotional Eater Questionnaire (EEQ)

Introduction: Emotions have a powerful effect on our choice of food and eating habits. It has been found that in some people there is relationship between eating, emotions and the increased energy intake. This relationship should be measurable to better understand how food is used to deal with certain mood states and how these emotions affect the effectiveness of weight loss programs. Objective: To develop and analyze the psychometric characteristics of a questionnaire on emotional eating for obesity easy to apply in clinical practice. Subjects and methods: A ten-item questionnaire called Emotional-Eater-Questionnaire (EEQ) was developed and administered to a total of 354 subjects (body mass index, 31 ± 5), aged 39 ± 12, who were subjected to a weight-reduction program. The questionnaire was specifically designed for obesity. Analysis of the internal structure, internal consistency, test-retest reliability and convergent validity with Mindful-Eater-Questionnaire (MEQ) were conducted. Results: After principal components analysis, the questionnaire was classified in three different dimensions that explained 60% of the total variance: Disinhibition, Type-of-food and Guilt. Internal consistency showed that Cronbach's alpha was 0.773 for the "Dishinibition" subscale, 0.656 for the "Type of food" subscale and 0.612 for the "Guilt" subscale. The test-retest stability was r =0.70. The data showed that the percentage of agreement between the EEQ and the MEQ was around 70% with a Kappa index of 0.40; P < 0.0001. Conclusion: We have presented a new questionnaire, which classifies individuals as a function of the relation between food intake and emotions. Such information will permit personalised treatments to be designed by drawing up early strategies from the very beginning of treatment programmesIntroducción: Las emociones tienen un poderoso efecto sobre la elección de alimentos y los hábitos alimentarios. Existe una relación entre comer, emociones y el aumento del aporte calórico. Esta relación debería ser medible para comprender mejor cómo utilizamos los alimentos en determinados estados de ánimo y cómo las emociones afectan a la eficacia de los programas de pérdida de peso. Objetivo: Desarrollar y analizar las características psicométricas de un cuestionario para identificar la ingesta emocional en la obesidad de fácil aplicación en la práctica clínica. Material y métodos: Se ha desarrollado y administrado un cuestionario de diez ítems llamado Cuestionario-de-Comedor-Emocional (CCE) a un total de 354 sujetos (Índice de Masa Corporal: 31 ± 5), (Edad: 39 ± 12 años), pertenecientes a un programa de reducción de peso. Se llevó a cabo un análisis de la estructura interna del cuestionario, de la consistencia interna, la fiabilidad testretest y la validez convergente con el Mindful-Eater- Questionnaire (MEQ). Resultados: El análisis de componentes principales del cuestionario encontró tres dimensiones diferentes que explicaban el 60% de la varianza: desinhibición, tipo de alimento y culpa. La consistencia interna mostró que el alfa de Cronbach fue de 0,773 para la subescala "Desinhibición", 0,656 para "Tipo de alimentos" y 0,612 para "culpa". La estabilidad test-retest fue de r = 0,70. Los datos mostraron que el porcentaje de acuerdo entre el CCE y MEQ era del 70% con un índice Kappa de 0,40, P < 0,0001. Conclusión: Hemos presentado un nuevo cuestionario, que clasifica a los individuos en función de la relación entre la ingesta de alimentos y las emociones. Esta información permitirá el diseño de tratamientos personalizados desde el inicio para la obesida

CLOCK, PER2 and BMAL1 DNA methylation: association with obesity and metabolic syndrome characteristics and monounsaturated fat intake

The circadian clock system instructs 24-h rhythmicity on gene expression in essentially all cells, including adipocytes, and epigenetic mechanisms may participate in this regulation. The aim of this research was to investigate the influence of obesity and metabolic syndrome (MetS) features in clock gene methylation and the involvement of these epigenetic modifications in the outcomes. Sixty normal-weight, overweight and obese women followed a 16-weeks weight reduction program. DNA methylation levels at different CpG sites of CLOCK, BMAL1 and PER2 genes were analyzed by Sequenom's MassARRAY in white blood cells obtained before the treatment. Statistical differences between normal-weight and overweight + obese subjects were found in the methylation status of different CpG sites of CLOCK (CpGs 1, 5-6, 8 and 11-14) and, with lower statistical significance, in BMAL1 (CpGs 6-7, 8, 15 and 16-17). The methylation pattern of different CpG sites of the three genes showed significant associations with anthropometric parameters such as body mass index and adiposity, and with a MetS score. Moreover, the baseline methylation levels of CLOCK CpG 1 and PER2 CpGs 2-3 and 25 correlated with the magnitude of weight loss. Interestingly, the percentage of methylation of CLOCK CpGs 1 and 8 showed associations with the intake of monounsaturated and polyunsaturated fatty acids. This study demonstrates for the first time an association between methylation status of CpG sites located in clock genes (CLOCK, BMAL1 and PER2) with obesity, MetS and weight loss. Moreover, the methylation status of different CpG sites in CLOCK and PER2 could be used as biomarkers of weight-loss success, particularly CLOCK CPGs 5-6

Stability of the timing of food intake at daily and monthly timescales in young adults

Cross-sectional observations have shown that the timing of eating may be important for health-related outcomes. Here we examined the stability of eating timing, using both clock hour and relative circadian time, across one semester (n = 14) at daily and monthly time-scales. At three time points ~ 1 month apart, circadian phase was determined during an overnight in-laboratory visit and eating was photographically recorded for one week to assess timing and composition. Day-to-day stability was measured using the Composite Phase Deviation (deviation from a perfectly regular pattern) and intraclass correlation coefficients (ICC) were used to determine individual stability across months (weekly average compared across months). Day-to-day clock timing of caloric events had poor stability within individuals (~ 3-h variation; ICC = 0.12–0.34). The timing of eating was stable across months (~ 1-h variation, ICCs ranging from 0.54–0.63), but less stable across months when measured relative to circadian timing (ICC = 0.33–0.41). Our findings suggest that though day-to-day variability in the timing of eating has poor stability, the timing of eating measured for a week is stable across months within individuals. This indicates two relevant timescales: a monthly timescale with more stability in eating timing than a daily timescale. Thus, a single day’s food documentation may not represent habitual (longer timescale) patterns

Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy

<p>Abstract</p> <p>Background</p> <p>The epidermal specific ablation of <it>Trp53 </it>gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of <it>Rb </it>gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular features of some of these human malignancies.</p> <p>Results</p> <p>To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in additional mouse tumors using microarray analysis. Two of the genes of this signature, AURKA and UBE2C, were validated in human breast and cervical cancer as potential biomarkers of malignancy.</p> <p>Conclusions</p> <p>Our analyses demonstrate that these mouse models are promising preclinical tools aimed to search for malignancy biomarkers and to test targeted therapies of prospective use in human aggressive tumors and/or with p53 mutation or inactivation.</p

Fragmentation of daily rhythms associates with obesity and cardiorespiratory fitness in adolescents: The HELENA study

Background & aims: Chronobiology studies periodic changes in living organisms and it has been proposed as a promising approach to investigate obesity. We analyze the association of the characteristics of the rest-activity rhythms with obesity, cardiorespiratory fitness and metabolic risk in adolescents from nine European countries. Methods: 1044 adolescents (12.5-17.5 y) were studied. Circadian health was evaluated by actigraphy with accelerometers (Actigraph GT1M). Characteristics of the daytime activity such as fragmentation (intradaily variability), estimated acrophase, and 10 h mean daytime activity index were obtained. Body composition was assessed using Bioelectrical-Impedance-Analysis, skinfold thickness, air-displacement-plethysmography and Dual-energy-X-ray-Absorptiometry. Cardiorespiratory fitness (VO2max) and metabolic risk were studied. Results: Highly fragmented activity rhythms were associated with obesity and central adiposity (P < 0.05). Obese adolescents had-3 times higher odds of having a high fragmentation of daytime activity compared to normal weight adolescents OR (95% CI) = 2.8 (1.170, 6.443). A highly fragmented rhythm was also related to lower cardiorespiratory fitness and higher metabolic risk (P < 0.05) so those adolescents classified as low fitness showed a significantly higher fragmentation of daytime activity than those included in the high fitness group (P < 0.0001). Other characteristics of the rhythms such as smaller 10 h daytime mean activity index and delayed estimated acrophase were also related to obesity and metabolic risk (P < 0.05). Conclusions: Our results indicate that the daily organization of the rest-activity cycle is more fragmented in obese and less fit adolescents and correlates with higher metabolic risk. This fact reinforces our hypothesis that disturbances in daily rhythms can be considered as sensitive markers of poorer adolescent's health