Effects of pioglitazone on promoting energy storage, not expenditure, in brown adipose tissue of obese fa/fa Zucker rats: Comparison to CL 316,243

Recent advances in the treatment of non-insulin-dependent diabetes mellitus (NIDDM) include the use of thiazolidinediones (TZDs), agents that enhance insulin action, in part, through an activation of adipose tissue peroxisome proliferator-activated receptor gamma. Current evidence also indicates tha t these agents upregulate uncoupling protein 1 (UCP1) gene expression in br own adipocytes and increase interscapular brown adipose tissue (IBAT) mass in rodents, suggestive of a thermogenic component to their mechanism of act ion. In the present study, the TZD pioglitazone (PIO) and the beta(3)-adren oceptor agonist CL 316,243 (CL), were used to determine whether the antidia betic effects of PIG, like those of CL, may, in part, be mediated by an inc rease in either IBAT thermogenesis or whole-body energy expenditure. Treatm ent of obese, insulin resistant fa/fa Zucker rats with PIO for 10 days resu lted in a 2- to 3-fold increase in IBAT mass, due largely to an increase in adipocyte size and number, and increased fatty acid biosynthesis. However, unlike the effects of CL, the PIO-induced IBAT changes were not associated with an increase in UCP1 expression or whole-body energy expenditure. In c ontrast to CL, PIO substantially increased body weight gains over the 10-da y treatment period by increasing feeding efficiency. These data suggest tha t, unlike CL, the actions of PIO in the obese Zucker rat does not include i ncreased energy expenditure, but rather strengthens its role as an adipogen ic and lipogenic agent, which promotes energy storage. Copyright (C) 2000 b y W.B. Saunders Company.