Whole Body FFA Metabolism. R fa was substantially elevated in Obese compared to Lean confirming an earlier study [26] showing mobilization, rather impaired clearance, to be the main mechanism for fatty acid elevation in obese animals (Table 5). Tesaglitazar's influence on systemic FFA availability was highly dependent on prevailing insulin level. In the basal state plasma FFA levels were similar in Tesaglitazar and vehicle treated obese rats. Interestingly in this situation tesaglitazar treated animals actually exhibited elevated R fa compared to vehicle controls which did not translate into a further elevation in plasma FFA levels due to a treatment induced increase in K fa (Table 5), the combined ability of the tissues of the body to take up FFA. Tesaglitazar profoundly improved insulin's ability to suppress systemic FFA mobilization (R fa), the main mechanism of treatment induced FFA lowering. ClampL FFA levels in the Tesaglitazar group were in fact virtually normalized despite a 2.3-fold higher R fa compared to the Lean group, due to the treatment induced enhancement in K fa (Table 5).
