Regulation of gene expression by activation of the peroxisome proliferator-activated receptor γ with rosiglitazone (BRL 49653) in human adipocytes

To better define the mechanism of action of the thiazolidinediones, we incubated freshly isolated human adipocytes with rosiglitazone and investigated the changes in mRNA expression of genes encoding key proteins of adipose tissue functions. Rosiglitazone (10(-6) M, 4 h) increased p85 alpha phosphatidylinositol 3-kinase (p85 alpha PI-3K) and uncoupling protein-2 mRNA levels and decreased leptin. expression. The mRNA levels of insulin receptor, IRS-1, Glut 4, lipoprotein lipase, hormone-sensitive lipase, acylation-stimulating protein, fatty acid transport protein-1, angiotensinogen, plasminogen activator inhibitor-1, and PPAR gamma 1 and gamma 2 were not modified by rosiglitazone treatment. Activation of RXR, the partner of PPAR gamma, in the presence of rosiglitazone, increased. further p85 alpha PI-3K and UCP2 mRNA levels and produced a significant augmentation of Glut 4 expression. Because p85 alpha PI-3K is a major component of insulin action, the induction of its expression might explain, at least in part, the insulin-sensitizing effect of the thiazolidinediones. (C) 1999 Academic Press.