MOLECULAR PHARMACOLOGY, 50:1087-1094 (1996). Peroxisome Proliferator-Activated Receptor-y Activation by Thiazolidinediones Induces Adipogenesis in Bone Marrow

The thiazolidinediones improve insulin sensitivity in animal models and have promise as potent oral antidiabetic agents. Their clinical use has been limited because of the resulting anemia and cardiac hypertrophy. Some compounds of this class have been reported to induce bone marrow fat accumu-lation in animals, and this effect could account for the observed anemia. We examined the biological mechanism contributing to this phenomenon. The thiazolidinediones BRL49653 and pio-glitazone induced adipocyte differentiation in the BMS2 bone marrow stromal cell line in a dose- and time-dependent man-ner. These actions were further enhanced by the presence of glucocorticoids and other adipogenic agonists. The thiazo-lidinediones increased the mRNA levels of adipocyte-specific genes, including that of their receptor, the peroxisome prolif-erator-activated receptor--y (PPARy). In contrast, mRNA level