Tesaglitazar also augmented insulin's ability to quench systemic FFA availability and decrease FFA uptake, as well as incorporation into nonoxidative disposal in skeletal muscles, heart and the liver. Putting these effects together with the afore mentioned effects on glucose metabolism, it is apparent that tesaglitazar induced an effective and widespread improvement in the ability of insulin to switch fuel mixture in the tissues. This is illustrated in Figure 4 by the results at the level of the whole body, skeletal muscle, heart, and adipose tissue. Under basal insulin conditions, obese Zucker rats exhibited elevated rates of FFA utilization and storage in the majority of tissues driven by elevated circulating FFA levels, disturbances that were not affected by tesaglitazar (discussed below). The apparent failure of the substance to enhance tissue level FFA oxidation in the basal state (as suggested by unaltered FFA uptake in combination with unaltered FFA incorporation into nonoxidative disposal in skeletal muscle and liver) surprised us based on our expectation that tesaglitazar should increase fatty acid oxidation capacity via PPARα activation suggested by previous studies showing tesaglitazar induced
