ИСТИНА

Prep1 is a homeodomain transcription factor essential in development and in the adult. It was shown previously that Prep1 is required for the mouse embryonic development at very early stage (E6.5) (1). We are currently investigating a role of Prep1 in the development of adipose tissue. This is particular interesting in light of the recent publication about the role of Pbx1, the main Prep1 partner, in adipocyte development (2). We showed that Prep1 is indispensable for adipocyte differentiation. The downregulation of Prep1 expression by shRNA in mouse preadipocyte cell line (3T3 - L1) results in a sharp increase of differentiation potential. This effect was very robust and shown by the appearance of expression of specific adipocytic markers (PPARg, Ap2, Glut4). Prep1 seems to have a direct effect on the main adipocytic factors as their expression is increased even in homogenous population of differentiated mature adipocytes with reduced Prep1 expression levels. Similar results were obtained with ex-vivo isolated murine pre-adipocytes with Prep1 reduced expression level. We are also investigating molecular mechanisms of the observed effect of Prep1. Preliminary data show that Prep1 is required for the proper level of Akt phosphorylation as Prep1 downregulation results in at least two-fold increase of Akt phosphorylation level in preadipocytes. Our ongoing experiments are to uncover molecular players in pathways that can be affected by Prep1. Our recent work aimed at whole genome profiling of Prep1 in mES cells (the data are being prepared for publication) allows us to select several adipogenic pathways that may be dependent on Prep1. This research was supported by the grant from the Russian government (02.740.11.0872).