Effects of peroxisome proliferator-activated receptor α/δ agonists on HDL-cholesterol in vervet monkeys

The objective of this study was to demonstrate the efficacy of a novel peroxisome proliferator-activated receptor ( PPAR) agonist and known PPAR alpha and PPAR delta agonists to increase HDL-cholesterol (HDL-C) in the St. Kitts vervet, a nonhuman primate model of atherosclerosis. Four groups (n = 6) were studied and each group was assigned one of the following "treatments": a) vehicle only ( vehicle); b) the PPAR delta selective agonist GW501516 (GW); c) the PPAR alpha/delta agonist T913659 (T659); and d) the PPAR alpha agonist TriCor(R) (fenofibrate). No statistically significant changes were seen in body weight, total plasma cholesterol, plasma triglycerides, VLDL-C, LDL-C, or apolipoprotein B ( apoB) concentrations. Each of the PPAR alpha and PPAR delta agonists investigated in this study increased plasma HDL-C, apoA-I, and apoA-II concentrations and increased HDL particle size in St. Kitts vervets. The maximum percentage increase in HDL-C from baseline for each group was as follows: vehicle, 5%; GW, 43%; T659, 43%; and fenofibrate, 20%. Treatment with GW and T659 resulted in an increase in medium-sized HDL particles, whereas fenofibrate showed increases in large HDL particles. These data provide additional evidence that PPAR alpha and PPAR delta agonists ( both mixed and selective) have beneficial effects on HDL-C in these experimental primates.