NUTREPIGENOMICS · Early nutrition and long-term consequences on health and disease: an epigenetic approach
6РП — Действия „Мария Кюри“
- Период
- 2007-09-01 → 2009-08-31
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Храненето в ранното детство и неговото влияние върху риска от диабет се проучват чрез модел с мишки, при които преяждането предава заболяването на следващите поколения. Това помага да се разберат механизмите, чрез които епигенетичните промени пренасят метаболитни нарушения по мъжка линия.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - NUTREPIGENOMICS (Early nutrition and long-term consequences on health and disease: An epigenetic approach)
Epidemiologic evidence suggests that sub-optimal nutrition during foetal and/or postnatal development influence diabetes risk later in life. In addition, such environmentally-induced phenotypes may manifest in subsequent generations, even when the environmental triggers are not present anymore. Genomes may integrate nutritional variation into permanent changes in gene expression through epigenetic modifications, including DNA methylation and histone modifications. While epigenetic mechanisms have been widely studied in other ageing related disorders like cancer, little is known regarding the potential interplay between a) nutrition, b) mammalian development, c) epigenetic mechanisms and d) metabolic disorders, such as diabetes. We have developed a mouse model of intergenerational epigenetic inheritance of diabetes by manipulating nutrition of the parental cohort during development. Specifically, here we show that, in mice, overfeeding during early postnatal life programs adult obesity, insulin resistance and glucose intolerance in males. Furthermore, we show, for the first time, that offspring and grand-offspring from neonatally over nourished male mice also develop glucose intolerance by age 5-6 months. Across generation transmission of diabetic phenotype through the male lineage clearly suggests that the phenotype is transmitted through the gametes, likely due to epigenetic modifications. Clearly, our data suggest that nutritional challenges during critical periods of growth (i.e. foetal growth and early neonatal growth) may have metabolic consequences well beyond life span of affected individuals and manifest in subsequent generations. These studies will provide new insights into the mechanisms and dynamics underlying epigenetic inheritance of disease, with special emphasis on diabetes.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Human and animal studies suggest that nutritional imbalances occurring during fetal and early postnatal periods can have long-term consequences on health, including obesity and diabetes, and appear to be at least partly caused by changes in genomic expression.Genomes can integrate and translate environmental changes into stable modifications of gene expression by altering epigenetic marks. Epigenetic marks like DNA methylation are particularly important, because they are highly dependent on the availability of methyl donors that are supplied by the diet. Our hypothesis is that the mechanism involved in the long-term effects of nutrition is mediated by changes in the degree of DNA methylation, that in turn, cause permanent changes in gene expression.We propose to determine the genome-wide methylation profiling of liver samples from a mouse model of fetal undernutrition by using microarrays specific for CpG islands, because these are chromosomic regions that are susceptible to methylation and are physically associated to gene regulatory regions. We will also explore the role of diets supplemented with nutrient methyl donors in preventing/attenuating the phenotypes associated with fetal malnutrition.The presence of a link between nutrition, changes in DNA methylation and gene expression can have great clinical relevance, since the possibility of using dietary intervention to maintain the right degree of DNA methylation in order to prevent the deleterious metabolic effects, may become feasible.
Оригинален текст от CORDIS (на английски).
Участници
- HOSPITAL ST. JOAN DE DEU · ESPLUGUES DE LLOBREGATКоординаторНиво градИспания
Връзки
Данни: CORDIS, © Европейски съюз