PGC1B METSYND · PGC1beta coactivator and the Metabolic Syndrome:Functional characterisation in vivo using genetically modified mouse models.
6РП — Действия „Мария Кюри“
- Период
- 2006-01-01 → 2007-12-31
- Финансиране от ЕС
- 159 613 €
- Участници
- 1
- Схема
- SCF
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
Протеинът PGC1beta и неговата роля при развитието на затлъстяване и диабет се изучават чрез генетично модифицирани мишки. Резултатите помагат да се разбере как митохондриите осигуряват енергия в сърцето, черния дроб и мускулите при различни диети.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - PGC1B METSYND (PGC1beta coactivator and the Metabolic Syndrome:Functional characterisation in vivo using genetically modified mouse models)
Recently, the research team have demonstrated that a specific group of proteins termed PGCs are important for the function of mitochondria, the component of the cell that makes energy. Here we wanted to study, specifically if the loss of one of these proteins, so called PGC1beta have any effect in the development of obesity and diabetes. For this purpose, we used a genetically modified mouse model and a second to none batch of techniques to study it. Our results indicate that PGC1beta plays a role in controlling the activity of mitochondria (in many different organs) but seems that the deletion of this gene does not cause major metabolic failure as obesity and diabetes in normal conditions, because of a partial compensation mechanism due to their partner PGC1alpha in important metabolic tissues such as brown and white adipose tissue. Nevertheless, the loss of PGC1beta provokes several defects in other relevant tissues as skeletal muscle, heart and liver that were not recovered for PGC1alpha, specially when challenged with metabolic stressors (such as a high fat diet). Our results indicate that, although having some overlapping functions, PGC1beta seems to cover basal energetic needs whereas their partner PGC1alpha provides the extra energetic support required under conditions of increased energy demand.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Type 2 Diabetes mellitus (T2D) as part of the cluster of clinical disorders that define Metabolic Syndrome is characterised by a major failure of the mechanisms controlling fuel homeostasis secondary to ineffective insulin action in the context of insulin resistance and/or inappropriate insulin secretion. Recently it has been suggested that T2D is associated with a coordinated down-regulation of the coactivator PGC1alpha and its target genes involved in mitochondrial oxidative phosphorylation.PGC1beta, a ne w coactivator homologous to PGC1alpha, which is highly expressed in heart and skeletal muscle has been recently identified. We aim to understand the role of PGC1beta; in whole body energy homeostasis and its role in the development of the Metabolic Syndrom e, and more specifically in myocardium that according to our previous research may be important for diabetes and associated heart problems. Our strategy involves a) a loss of function experiment using a PGC1beta knock-out mouse, and b) a gain of function experiment using a striated muscle (heart and skeletal muscle) transgenic PGC1beta mouse. To investigate these aims we will use a multi-approach strategy that involves in vivo phenotyping of genetically modified mouse models combined with state of the art ex vivo molecular characterisation using profiling technologies (e.g gene expression profiling, proteomic and lipidomic technologies) and advanced bioinformatics analysis. These animal models will be challenged with specific environmental interventions (hi gh fat diet, exercise) to challenge compensatory physiological mechanisms. Using these approaches we will gain insights through extensive characterisation into the global and cardiac functions of PGC1beta as integrator of specific energy homeostasis proces ses. The work will also allow, thanks to the novel multiapproach outlined, the first analysis in detail of the PGC1beta signalling and its metabolic effects.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR, MASTERS SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGEКоординаторНиво градОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз