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

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Expresión de genes reloj en el tejido adiposo humano : cambios en ritmos circadianos / Purificación Gómez Abellán; directores, Marta Garaulet Aza, Juan Antonio Madrid Pérez.

Texto en español e inglés.Tesis-Universidad de Murcia.MEDICINA ESPINARDO. DEPOSITO. MU-Tesis 872.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. TM 4357

Timing of Breakfast, Lunch, and Dinner. Effects on Obesity and Metabolic Risk

(1) Background: Eating is fundamental to survival. Animals choose when to eat depending on food availability. The timing of eating can synchronize different organs and tissues that are related to food digestion, absorption, or metabolism, such as the stomach, gut, liver, pancreas, or adipose tissue. Studies performed in experimental animal models suggest that food intake is a major external synchronizer of peripheral clocks. Therefore, the timing of eating may be decisive in fat accumulation and mobilization and affect the effectiveness of weight loss treatments. (2) Results: We will review multiple studies about the timing of the three main meals of the day, breakfast, lunch and dinner, and its potential impact on metabolism, glucose tolerance, and obesity-related factors. We will also delve into several mechanisms that may be implicated in the obesogenic effect of eating late. Conclusion: Unusual eating time can produce a disruption in the circadian system that might lead to unhealthy consequences

An approximation to the temporal order in endogenous circadian rhythms of genes implicated in human adipose tissue metabolism

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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