MOLECULAR MECHANISM OF ADIPOGENIC ACTIVATION OF THE ANGIOTENSINOGEN GENE

Angiotensinogen gene expression is controlled in a tissue- and develop ment-specific manner. Interestingly, the angiotensinogen gene is abund antly expressed in adipose tissues other than the liver, where it is m ainly produced. We investigated the molecular mechanism of angiotensin ogen gene expression in a 3T3-L1 preadipocyte-adipocyte system. Althou gh angiotensinogen mRNA was barely detectable in preadipocytes, its le vels increased significantly during differentiation. As a whole, the p attern of the change in transcriptional activity of the angiotensinoge n promoter was similar to that of the angiotensinogen mRNA levels duri ng adipogenic differentiation, indicating that the activation of the a ngiotensinogen promoter might be involved in the adipogenic differenti ation-coupled gene expression. The proximal promoter region, from -96 to +22 of the transcriptional start site, was sufficient to confer adi pogenic activation, and the proximal element from -96 to -52 of the tr anscriptional start site was necessary for this promoter stimulation. DNA-protein binding experiments showed that this proximal element spec ifically bound to a nuclear factor induced by adipogenic differentiati on. These results suggest that the proximal promoter element from -96 to -52 plays a role in adipogenic activation of the angiotensinogen pr omoter.