HIF IN ADIPOSE BIOLO · Manipulating Hypoxia Inducible Factor (HIF) activity in the adipose cell. A means of altering cell differentiation and metabolism ?
6РП — Действия „Мария Кюри“
- Период
- 2003-12-01 → 2005-11-30
- Финансиране от ЕС
- 159 046 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите.
Накратко на български
Протеините от типа HIF влияят върху метаболизма на мазнините и глюкозата в мастните клетки. Разбирането на тези процеси помага за по-доброто изясняване на биологията на адипоцитите и борбата с разпространението на затлъстяването.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - HIF IN ADIPOSE BIOLO (Manipulating Hypoxia Inducible Factor (HIF) activity in the adipose cell. A means of altering cell differentiation and metabolism)
The Marie Curie project consisted in studying the role of hypoxia inducible factor (HIF) pathway in fat and glucose metabolism. Even though some publications suggested that the HIF pathway could have a role, nothing was clearly demonstrated by the time of the project elaboration. We first of all defined the various components of the HIF system, including HIF-alpha isoforms and HIF hydroxylases, and their level of expression during the course of 3T3-L1 adipose differentiation. One of our main findings was that HIF-2alpha expression was significantly increased by differentiation in normoxia and was surprisingly decreased by hypoxia in differentiated cells, whereas HIF-1alpha was not affected by hypoxia in differentiated 3T3-L1 cells. In parallel, we focussed on the expression of key genes implicated in adipose differentiation and function. We observed, as expected, an increase of GLUT-1 mRNA level under hypoxic conditions in differentiated cells. The expression of lipoprotein lipase (LPL) and hormone sensitive lipase (HSL) did not seem to be affected by hypoxia in differentiated 3T3-L1 cells. Interestingly, we found a massive decrease of fatty acyl synthase (FAS) messenger ribonucleic acid (mRNA) level as well as of adiponectin (ACRP30), which could be related to the changing of HIF-alpha proteins in the differentiated 3T3-L1 cells. The latter was a particularly exciting finding, opening up new perspectives for understanding the cell biology of adipocytes, representing a key to coping with the epidemic of obesity which is currently spreading around the world.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
In most individuals, the adipose tissue, like other adult tissues, maintains a stable mass. Nevertheless, this tissue displays a unique capacity to grow or regress during adulthood, when energy balance shifts positively or negatively. In humans, phenotypes of adipose dystrophy range from massive obesity, where adipose mass represents 60 to 70% of body weight, to lipoatrophy, with less than 2% of fat. Starting during the past 10-20 years, the number of obese individuals is increasing on an epidemic scale wor ld-wide. The clinical problem of excessive adipose tissue mass resides in its strong association with a number of life-threatening conditions: hyperlipidemia, high blood pressure, glucose intolerance and diabetes, coronary heart disease and some types of c ancers.The main cellular components of adipose tissue are adipocytes. It is now recognised that these cells are at the heart of a complex endocrine and paracrine network, which substantially influences the whole organism. Dysregulation of adipose cell mass induces profound alterations of the cell\'s metabolic properties and hormonal responsiveness, leading to alteration in adipose-derived circulating factors. These defects have been causally implicated in several obesity-related co-morbidities.We and others have recently revealed that adipose differentiation, metabolism and secretory function are sensitive to hypoxia and that Hypoxia Inducible Factor (HIF) activation underlies several ol these responses. Here, we propose to investigate the genomic and phenot ypic effects of modulation of HIF activity in the adipose cell. At the cellular level, the effect of genetic and pharmacological activation of the HIF system on adipose gene expression and metabolic activity will be studied in the mouse 3T3-L1 pre-adipose cell line. The physiological effects of manipulating HIF will also be investigated in transgenic mice with enhanced HIF activity specifically in the adipose tissue.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OXFORDКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз