The effects of tesaglitazar on glucose and lipid metabolism in the obese Zucker rat [16] have generally proven to be predictive of effects in patients with type 2 diabetes [30] and obese/insulin resistant subjects [28, 29, 40], with improvements in glucose tolerance, lipid tolerance, insulin sensitivity, and meal induced FFA lowering, as well as decreased plasma TG levels and decreased apoCIII levels seen in both humans and rodents. One aspect of glucose metabolism that tesaglitazar did not correct in the obese Zucker rats was the defect in basal HGO, substantially elevated in obese compared to lean Zucker rats (Figure 1). This may have been a consequence of the failure of treatment to lower plasma FFA flux into the liver in this state (Figure 4). This was probably a result of the lack of lowering of plasma FFA level in the basal state which represents a clear departure from the response in clinical studies where overnight fasting FFAs were consistently lowered by tesaglitazar [28–30]. One possible explanation may be the relatively short treatment duration in the current study. In response to
