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.
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.