Rosiglitazone decreases cellular iron status in livers from zdf rats (LB774)

Recent work has linked increased circulating iron and cellular iron status with insulin resistance and type 2 diabetes. An increase in cellular iron is also associated with chronic inflammation. To further explore this association we examined free iron, and proteins important for cellular iron management, in liver tissue from Zucker Diabetic Fatty (ZDF) rats and ZDF rats treated with Rosiglitazone (ZDF ROSI). Rosiglitazone (ROSI) is known to improve insulin sensitivity and has recently been shown to reduce certain inflammatory signals. We hypothesized that ROSI treatment of ZDF rats would cause a reduction in free iron and related changes in proteins involved in cellular iron regulation. Six week old ZDF rats were fed ad libitum a chow diet or a chow diet with 100 mg of ROSI/kg of diet for 6 weeks. The free iron concentration in liver tissue was reduced by 26% ± 4% (p=0.02) in response to ROSI treatment compared to ZDF controls. Ferritin protein levels in ZDF ROSI were significantly reduced by 37% ± 12% (p=.003) compared to ZDF. Iron regulatory protein (IRP) analysis showed a reduction in IRP by 21% ± 7% (p=.03) in ZDF ROSI compared to ZDF Chow. These results are consistent with a potential anti‐inflammatory effect of ROSI treatment on the iron status of liver tissue.