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

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

Timing of food intake is associated with weight loss evolution in severe obese patients after bariatric surgery

Background Recent research has demonstrated a relationship between the timing of food intake and weight loss in humans. However, whether the meal timing can be associated with weight loss in patients treated with bariatric surgery is unknown. Objective To evaluate the role of food-timing in the evolution of weight loss in a sample of 270 patients that underwent bariatric surgery with a follow-up of 6 years. Methods Participants (79% women; age [mean ± SD]: 52 ± 11 years; BMI: 46.5 ± 6.0 kg/m2) were classified according their weight loss response patterns after bariatric surgery: good weight-loss-responders (67.8%), primarily poor weight-loss-responders (10.8%) or secondarily poor weight-loss-responders (21.4%). Then, they were grouped in early-eaters and late-eaters, according to the timing of the main meal (before or after 15:00 h). Obesity and biochemical parameters, energy and macronutrients intake, energy expenditure, sleep duration, and chronotype were studied. Results The percentage of late eaters (after 15:00 h) was significantly higher in the primarily poor weight-loss-responders (∼70%) than in both secondarily poor weight-loss-responders (∼42%) and good weight-loss-responders (∼37%) (p = 0.011). Consistently, primarily poor weight-loss-responders had lunch later as compared to good and secondarily poor weight-loss-responders (p = 0.034). Age, gender and type of surgery were not determining. Surprisingly, obesity-related variables, biochemical parameters, pre-surgical total energy expenditure, sleep duration, chronotype, calorie intake and macronutrients distribution, were similar among groups. Conclusions Weight loss effectiveness after bariatric surgery is related to the timing of the main meal. Our preliminary results suggest that the timing of food intake is important for weight regulation and that eating at the right time may be a relevant factor to consider in weight loss therapy even after bariatric surgery

MTNR1B type 2 diabetes genetic risk, shift work, and morningnesseveningness preference

Night shift work, behavioral rhythms, and the common MTNR1B risk single nucleotide polymorphism (SNP), rs10830963, associate with type 2 diabetes, however, whether they exert joint effects to exacerbate type 2 diabetes risk is unknown. Among employed participants of European ancestry in the UK Biobank (N=189,488), we aimed to test the cross-sectional independent associations and joint interactions of these risk factors on odds of type 2 diabetes (n=5,042 cases) and HbA1c levels (n=175,156). Current shift work, definite morning or evening preference, and MTNR1B rs10830963 risk-allele associate with type 2 diabetes and HbA1c levels. The effect of rs10830963 was not modified by shift work schedules. While marginal evidence of interaction between selfreported morningness-eveningness preference and rs10830963 was seen on risk of type 2 diabetes, this interaction did not persist when analysis was expanded to include all participants regardless of employment status and when using accelerometer-derived sleep-midpoint as an objective measure of morningness-eveningness preference. Our findings suggest that the MTNR1B risk-allele carriers may not have greater vulnerability to shift work or morningness-eveningness preference

Una aproximación al conocimiento de las bases moleculares de la obesidad y su relación con la distribución del tejido adiposo / Marta Garaulet Aza ; Directores: Salvador Zamora Navarro, Francisco Javier Tebar Massó.

Tesis - Universidad de Murcia.MEDICINA ESPINARDO. DEPOSITO. MU-Tesis 590.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. T.M.-1820

Effect of protein hydrolysis on the dialysability of amino acids and minerals in infant formulas

The objectives of this study were to evaluate the dialysed quantities of amino acids and minerals (calcium, phosphorus, magnesium, iron and zinc) in two types of infant formulas, one with a basis of native cow milk proteins and the other highly hydrolysed, to evaluate the possible application of Miller's in vitro method in amino acid and mineral availability studies. The percentage of dialysis differed between proteins. The hydrolysis treatment applied to the proteins significantly increased the dialysis percentage of almost all the amino acids. The dialysability of all the minerals was statistically greater in the formula made with a basis of hydrolysed proteins. Miller's method was seen to be of use for showing the effect which the hydrolysis treatment has on the availability of amino acids. Despite its limitations of having to be carried out in vitro, the study suggests that the nutritional value in relation with amino acids, minerals and trace elements differs between the both types of formulas.En el presente estudio, se evalúan las cantidades dializadas de aminoácidos y minerales (calcio, fósforo, magnesio, hierro y cinc) en dos tipos de fórmulas infantiles, ambas elaboradas a base de proteínas de leche de vaca, una con proteínas intactas o nativas y otra con proteínas altamente hidrolizadas, para valorar la posible aplicación del método in vitro de Miller en estudios de disponibilidad de aminoácidos y minerales. El porcentaje de diálisis difiere entre proteínas. El tratamiento de hidrólisis aplicado a las proteínas incrementó significativamente el porcentaje de diálisis de la mayoría de los aminoácidos. La cantidad dializada de todos los minerales estudiados fue estadísticamente superior en la fórmula elaborada con proteínas hidrolizadas. El método de Miller se ha mostrado efectivo para demostrar el efecto que el tratamiento de hidrólisis tuvo sobre la disponibilidad de aminoácidos. A pesar de las limitaciones que la utilización de un método in vitro implican, el estudio sugiere que el valor nutricional entre ambos tipos de fórmulas difiere en lo que se refiere a aminoácidos, minerales y elementos traz

Clucocorticoids Affect 24h Clock Genes Expression in Human Adipose Tissue Explant Cultures

Aims to examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock genes expression. Subjects and Methods VAT and SAT biopsies were obtained from morbid obese women (body mass index≥40 kg/m2) (n = 6). In order to investigate rhythmic expression pattern of clock genes and the effect of DEX on CLOCK, PER2 and BMAL1 expression, control AT (without DEX) and AT explants treated with DEX (2 hours) were cultured during 24 h and gene expression was analyzed at the following times: 10:00 h, 14:00 h, 18:00 h, 22:00 h, 02:00 h and 06:00 h, using qRT-PCR. Results CLOCK, BMAL1 and PER2 expression exhibited circadian patterns in both VAT and SAT explants that were adjusted to a typical 24 h sinusoidal curve. PER2 expression (negative element) was in antiphase with respect to CLOCK and in phase with BMAL1 expression (both positive elements) in the SAT (situation not present in VAT). A marked effect of DEX exposure on both positive and negative clock genes expression patterns was observed. Indeed, DEX treatment modified the rhythmicity pattern towards altered patterns with a period lower than 24 hours in all genes and in both tissues. Conclusions 24 h patterns in CLOCK and BMAL1 (positive clock elements) and PER2 (negative element) mRNA levels were observed in human adipose explants. These patterns were altered by dexamethasone exposure