Epigenética y obesidad / Epigenetics and obesity

La evidencia indica que la exposición a diversas condiciones ambientales en etapas tempranas de la vida puede inducir alteraciones persistentes en el epigenoma. Los estudios epigenómicos en sujetos obesos han permitido evaluar el papel de los mecanismos epigenéticos en el origen y desarrollo de la obesidad. La presente revisión aborda estudios que dan cuenta de la asociación entre la obesidad y metilación global del genoma (ADN), analizando el potencial impacto de intervenciones previas y posteriores al nacimiento que afectan la metilación del ADN y la obesidad en etapas más avanzadas de la vida. Estudios realizados principalmente en leucocitos, han logrado identificar sitios del ADN diferencialmente metilados asociados con obesidad. Estudios hasta la fecha no han demostrado que dichos cambios en metilación sean revertidos luego de bajar de peso. Esto contrasta con resultados iniciales en este campo, que sugieren que existirían marcadores epigenéticos presentes desde el nacimiento que permitirían definir el riesgo de obesidad durante el curso de la vida. La evidencia actual sugiere que algunas marcas epigenéticas son modificables, basándonos en la exposición en la vida intrauterina y también por los hábitos dietarios y de actividad fisica durante las etapas del crecimiento y en la adultez. Esto sugiere que existe la oportunidad de intervenir durante la gestación o en la vida posnatal temprana, que modificaría los perfiles epigenéticos desfavorables e idealmente contribuiría a prevenir la obesidad en los sujetos o poblaciones susceptibles.

Current evidence supports the notion that exposure to various environmental conditions in early life may induce permanent changes in the epigenome that persist throughout the life-course. This article focuses on early changes associated with obesity in adult life. A review is presented on the factors that induce changes in whole genome (DNA) methylation in early life that are associated with adult onset obesity and related disorders. In contrast, reversal of epigenetic changes associated with weight loss in obese subjects has not been demonstrated. This contrasts with well-established associations found between obesity related DNA methylation patterns at birth and adult onset obesity and diabetes. Epigenetic markers may serve to screen indivuals at risk for obesity and assess the effects of interventions in early life that may delay or prevent obesity in early life. This might contribute to lower the obesity-related burden of death and disability at the population level. The available evidence indicates that epigenetic marks are in fact modifiable, based on modifications in the intrauterine environment and changes in food intake, physical activity and dietary patterns patterns during pregnancy and early years of adult life. This offers the opportunity to intervene before conception, during pregnancy, infancy, childhood, and also in later life. There must be documentation on the best preventive actions in terms of diet and physical activity that will modify or revert the adverse epigenetic markers, thus preventing obesity and diabetes in suceptible individuals and populations.

Epigenética en enfermedades alérgicas y asma / Epigenetics in allergic diseases and asthma

Las enfermedades alérgicas y el asma son el resultado de complejas interacciones entre la predisposición genética y factores ambientales. El asma es una de las enfermedades crónicas más prevalentes en niños. En este artículo se revisan algunos factores ambientales como la exposición a alérgenos, tabaco, bacterias, componentes microbianos, dieta, obesidad y estrés, que intervienen durante la vida intrauterina y la infancia en la regulación epigenética de las enfermedades alérgicas y el asma. La revisión se realiza en tres tipos de modelos: in-vitro, animales y humanos.

Allergic diseases and asthma are the result of complex interactions between genetic predisposition and environmental factors. Asthma is one of the most prevalent chronic disease among children. In this article we review some environmental factors like: allergen exposition, tobacco, bacteria, microbial components, diet, obesity and stress, which influences during intrauterine and infancy life in the epigenetic regulation of asthma and allergic diseases. The review has been done in three models: in-vitro, animal and human.

Conceptos generales de epigenética: proyecciones en pediatría / General concepts of epigenetics: projections in paediatrics

La asociación entre factores ambientales presentes durante el desarrollo embrionario/fetal y enfermedades que puedan presentarse durante la vida representa un campo de creciente interés. En este contexto la evidencia actual apoya fuertemente que alteraciones en el crecimiento intrauterino y durante los primeros años de vida presentan una fuerte influencia en el riesgo de padecer enfermedades crónicas que en muchos casos pudiera ser mayor que la carga genética del paciente. La persistencia y reproducibilidad de los fenotipos asociados a alteraciones en el desarrollo temprano sugieren la participación de mecanismos moleculares que registran dichas modificaciones (i.e. mecanismos epigenéticos) generando una «reprogramación¼ celular y fisiológica. Esta revisión es la introducción a una serie de 5 artículos en torno a la participación de los mecanismos epigenéticos en el desarrollo de enfermedades crónicas (i.e. cardiovasculares, metabólicas, asma/alergias y cáncer) y su relación con el origen de dichas enfermedades en etapas tempranas del desarrollo. El objetivo de esta serie es mostrar el estado actual de esta área de la investigación y presentar los desafíos e interrogantes futuros en los cuales la pediatría tiene un papel preponderante, desarrollando estrategias para la prevención, detección precoz y seguimiento.

Current evidence supports the notion that alterations in intrauterine growth and during the first years of life have a substantial effect on the risk for the development of chronic disease, which in some cases is even higher than those due to genetic factors. The persistence and reproducibility of the phenotypes associated with altered early development suggest the participation of mechanisms that would record environmental cues, generating a cellular reprogramming (i.e. epigenetic mechanisms). This review is an introduction to a series of five articles focused on the participation of epigenetic mechanisms in the development of highly prevalent chronic diseases (i.e. cardiovascular, metabolic, asthma/allergies and cancer) and their origins in the foetal and neonatal period. This series of articles aims to show the state of the art in this research area and present the upcoming clues and challenges, in which paediatricians have a prominent role, developing strategies for the prevention, early detection and follow-up.

Microtubule proteins and their post-translational forms in the cerebrospinal fluid of patients with paraparesis associated with HTLV-I infection and in SH-SY5Y cells: An in vitro model of HTLV-I-induced disease

HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is characterized by axonal degeneration of the corticospinal tracts. The specific requirements for transport of proteins and organelles to the distal part of the long axon are crucial in the corticospinal tracts. Microtubule dysfunction could beinvolved in this disease, configuring an axonal transport disease. We measured tubulin and its posttranslational modified forms (acetylated and tyrosinated) in CSF of patients and controls, as well as tau and its phosphorylated forms. There were no significant differences in the contents of tubulin and acetyl-tubulinbetween patients and controls; tyrosyl-tubulin was not detected. In HAM/TSP, tau levels were significantly reduced, while the ratio of pT181/total tau was higher in patients than in controls, this being completely different from what is reported in other neurodegenerative diseases. Phosphorylation at T181 was also confirmed by Mass Spectrometry analysis. Western Blotting with monospecific polyclonal antibodies against pS199, pT205, pT231, pS262, pS356, pS396, pS404 and pS422 did not show differences in phosphorylation in these residues between patients and controls. Treating human SH-SY5Y neuroblastoma cells, a well-known in vitro neurite retraction model, with culture supernatant of MT-2 cells (HTLV-I infected cell line that secretes theviral Tax protein) we observed neurite retraction and an increase in tau phosphorylation at T181. A disruptionof normal phosphorylation of tau protein in T181 could result in its dysfunction, contributing to axonal damage.