|Wang, Fei - Children'S Nutrition Research Center (CNRC)|
|Tong, Qiang - Children'S Nutrition Research Center (CNRC)|
Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/8/2008
Publication Date: 5/7/2008
Citation: Wang, F., Tong, Q. 2008. Transcription factor PU.1 is expressed in white adipose and inhibits adipocyte differentiation. American Journal of Physiology. 295:C213-C220
Interpretive Summary: It is important to study the process of fat cell (adipocyte) formation, since this will provide insights into the development of obesity. Previously, we and others have found that GATA-2 and C/EBPalpha regulatory proteins change this process. It was known that PU.1 protein interacts with both GATA-2 and C/EBPalpha. But it is not known whether PU.1 plays any role in fat cells. We found that PU.1 gene is expressed in the fat tissue and fat cells. We also found that PU.1 suppresses fat cell formation when we over-expressed it. PU.1 does so by functioning together with GATA-2 to suppress the action of C/EBPalpha and C/EBPBeta, two key regulators directing fat cell formation. Furthermore, we found that the level of PU.1 is greatly increased in the fat of obese mice. These findings offer the first identification of PU.1's function in fat cells and may provide novel ways for the treatment of obesity.
Technical Abstract: PU.1 transcription factor is a critical regulator of hematopoiesis and leukemogenesis. Because PU.1 interacts with transcription factors GATA-2 and C/EBPa, both of which are involved in the regulation of adipogenesis, we investigated whether PU.1 also plays a role in the regulation of adipocyte differentiation. Our data indicate that PU.1 is expressed in white adipose tissue. PU.1 protein can also be detected in cultured 3T3-L1 adipocytes. Forced expression of PU.1 in 3T3-L1 cells inhibits adipocyte differentiation, while deletion of the transactivation domain of PU.1 abolishes this effect. The inhibition of adipocyte differentiation by PU.1 is achieved, at least in part, through repression of the transcriptional activity of C/EBPa and C/EBP'. Furthermore, GATA-2 and PU.1 have an additive inhibitory effect on C/EBP transactivation and adipogenesis. Finally, the expression of PU.1 is increased in white adipose of obese mice.