Peroxisome proliferator-activated receptor-gamma activation by thiazolidinediones induces adipogenesis in bone marrow stromal cells.

摘要: 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 cardiac hypertrophy. Some compounds this class reported to induce bone marrow fat accumulation animals, effect could account for observed anemia. We examined biological mechanism contributing phenomenon. BRL49653 pioglitazone induced adipocyte differentiation BMS2 stromal cell line a dose- time-dependent manner. These actions were further enhanced by presence glucocorticoids other adipogenic agonists. increased mRNA levels adipocyte-specific genes, including that their receptor, peroxisome proliferator-activated receptor-gamma (PPAR gamma). In contrast, genes encoding PPAR family members alpha, delta, or NUC-1) unchanged decreased. Thiazolidinedione treatment primary cells elicited comparable dose-dependent response. Using polyclonal antibody, gamma was detected protein lysates from adipose-rich marrow. Thus, thiazolidinedione directly regulates differentiation; expression may play key regulatory role process.