Many of the beneficial effects of tesaglitazar on glucose and lipid metabolism may be secondary to its effect on FFA exchange in adipose tissue. Specifically, fatty acid overflow into nonadipose tissues is ameliorated by two mechanisms: an enhanced ability of fat tissue to take up FFA [34], as well as a greater ability of postprandial insulin levels to suppress FFA appearance rate (Figure 4, middle panel). This latter effect is probably a result of more effective suppression of FFA release from adipocytes, but perhaps also due to reduced spillover of products of intravascular lipolysis into the systemic circulation. Similar effects on adipose tissue FFA exchange have been observed with a thiazolidinedione [26] but were not observed with a selective PPARα agonist (unpublished observations). Whether these actions are mediated via PPARγ agonism or alternatively more recently suggested molecular targets of thiazolidinediones [35, 36] remains to be determined.
