Genes Clock. Ritmos circadianos y predisposición a obesidad

Our physiology changes throughout the day and several physiological hormones display circadian rhythmicity. The alteration of this normal pattern is called chronodisruption (CD). In recent years it has been demonstrated that CD is related to obesity. Although several factors may be causing CD, one important aspect to consider is the failure in our internal clock. Indeed, studies performed in mutant animals have demonstrated that mutations in clock genes are related to obesity. In humans, mutations are rare (<1% of the population). Nevertheless, it is rather common to have genetic variations in one single nucleotide (SNP) which underlie differences in our vulnerability to disease. Several SNPs in clock genes are related to obesity and weight loss. Taking into account that genetics is behind CD, the questions is: are we predestinated? We will see along these lines that nutrigenetics and epigenetics answer: “NO, we are not predestinated”. Through nutrigenetics we know that our behaviours may interact with our genes and may decrease the deleterious effect of one specific risk variant. From epigenetics the message is even more positive: it is demonstrated that by changing our behaviours we can change our genome. Herein, we propose modifying “what, how, and when we eat” as an effective tool to decrease our genetic risk, and as a consequence to diminish CD and decrease obesity. This is a novel and very promising area in obesity prevention and treatment.Nuestra fisiología cambia durante el día y diversas hormonas muestran ritmicidad circadiana. La alteración de este patrón normal se denomina Cronodisrupción (CD). Recientemente se ha demostrado que la CD se relaciona con la obesidad. Aunque existen diversos factores que producen la CD, un aspecto importante a considerar es el fallo en nuestro reloj interno. Así, estudios realizados en animales de experimentación muestran que mutaciones en los genes reloj se asocian a la obesidad. En humanos estas mutaciones son poco frecuentes (<1% de la población). Sin embargo, es bastante común tener variaciones genéticas en un solo nucleótido (SNP) que explican las diferencias en nuestra vulnerabilidad a la enfermedad. Se conocen varios SNPs en los genes reloj que se asocian a la obesidad y a la pérdida de peso. Teniendo en cuenta que la genética está detrás de la CD, la cuestión es: ¿estamos predestinados? A lo largo de estas líneas descubriremos cómo la respuesta nutrigenética y epigenética es: “NO, no estamos predestinados”. A través de la nutrigenética sabemos que nuestros comportamientos pueden interactuar con nuestros genes y pueden disminuir el efecto nocivo de una variante de riesgo específico. A partir de la epigenética el mensaje es más positivo: al cambiar nuestros comportamientos podemos cambiar nuestro genoma. Según esto, proponemos modificar el "qué, cómo y cuándo comemos" como una herramienta eficaz para disminuir nuestro riesgo genético, y así disminuir la CD y la obesidad. Es por tanto esta un área muy novedosa y prometedora en la prevención y tratamiento de la obesidad

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

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

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

Composición en ácidos grasos de las margarinas de mayor consumo en España y su importancia nutricional

This study examines the fatty acid composition of margarines of major consumption in Spain in 2000. All the margarines contained at least 20% of linoleic acid, the average content of this fatty acid being 38%. Saturated fatty acids (lauric and miristic acids) did not exceed 4 % of the total fatty acid content. Most of the margarines analyzed contained less than 5% trans C18:1, although this content varied greatly among margarines (coefficient of variation: 112%) being median value 2.5%; polyunsaturated trans C18:2 and trans C18:3 did not represent more than 1 %. Nutritionally important ratios like saturated/unsaturated fatty acids, thrombogenicity and atherogenicity indexes were lower than 0.5. The findings suggest that Spanish margarines have moved to becoming products with a potentially healthier distribution of fatty acids. Even so, the great variability shown in fatty acid composition of margarines and poor labeling, highlight the importance of greater consumer information to avoid upsetting the traditional Mediterranean diet of SpainEste estudio examina la composición de ácidos grasos de las margarinas de mayor consumo en España en el año 2000, incluyendo ácidos grasos trans. Todas las margarinas contenían al menos 20% de linoleico, siendo el contenido medio del 38%. Los ácidos grasos saturados (laúrico y mirístico) no sobrepasaron el 4% del total de ácidos grasos. La mayoría de las margarinas contenían menos del 5 % de ácidos grasos trans C18:1, aunque la variabilidad era elevada entre las distintas marcas (coeficiente de variación:112 %), siendo la mediana del 2.5 %; los ácidos grasos trans poliinsaturados C18:2 y C18:3 no representaron más del 1 %. Índices nutricionalmente importantes como el cociente ácidos grasos saturados/insaturados, índices trombogénico y aterogénico, fueron menores de 0,5. Los resultados sugieren que las margarinas españolas muestran un cambio hacia una distribución de ácidos grasos más saludable, aunque debido a la gran variabilidad en su composición, la información del etiquetado debe mejorar para evitar perturbaciones en la tradicional dieta Mediterránea de España

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

Early Appearance of Epicardial Adipose Tissue through Human Development

Background: Epicardial adipose tissue (EAT) is a visceral fat depot with unique anatomic, biomolecular and genetic features. Due to its proximity to the coronary arteries and myocardium, dysfunctional EAT may contribute to the development and progression of cardiovascular and metabolic-related adiposity-based chronic diseases. The aim of this work was to describe, by morphological techniques, the early origin of EAT. Methods: EAT adipogenesis was studied in 41 embryos from 32 gestational days (GD) to 8 gestational weeks (GW) and in 23 fetuses until full term (from 9 to 36 GW). Results: This process comprises five stages. Stage 1 appears as mesenchyme at 33–35 GD. Stage 2 is characterized by angiogenesis at 42–45 GD. Stage 3 covers up to 34 GW with the appearance of small fibers in the extracellular matrix. Stage 4 is visible around the coronary arteries, as multilocular adipocytes in primitive fat lobules, and Stage 5 is present with unilocular adipocytes in the definitive fat lobules. EAT precursor tissue appears as early as the end of the first gestational month in the atrioventricular grooves. Unilocular adipocytes appear at the eighth gestational month. Conclusions: Due to its early origin, plasticity and clinical implications, factors such as maternal health and nutrition might influence EAT early development in consequence