Effects of the PPAR-δ agonist MBX-8025 on atherogenic dyslipidemia

Objective: Determine the effects of treatment with a selective PPAR-delta agonist +/- statin on plasma lipoprotein subfractions in dyslipidemic individuals. Methods: Ion mobility analysis was used to measure plasma concentrations of subfractions of the full spectrum of lipoprotein particles in 166 overweight or obese dyslipidemic individuals treated with the PPAR-delta agonist MBX-8025 (50 and 100 mg/d) +/- atorvastatin (20 mg/d) in an 8-week randomized parallel arm double blind placebo controlled trial. Results: MBX-8025 at both doses resulted in reductions of small plus very small LDL particles and increased levels of large LDL, with a concomitant reduction in large VLDL, and an increase in LDL peak diameter. This translated to reversal of the small dense LDL phenotype (LDL pattern B) in similar to 90% of the participants. Modest increases in HDL particles were confined to the smaller HDL fractions. Atorvastatin monotherapy resulted in reductions in particles across the VLDL-IDL-LDL spectrum, with a significantly smaller reduction in small and very small LDL vs. MBX-8025 100 mg/d (-24.5 +/- 5.3% vs. -47.8 +/- 4.9%), and, in combination with MBX-8025, a reversal of the increase in large LDL. Conclusion: PPAR-delta and statin therapies have complementary effects in improving lipoprotein subfractions associated with atherogenic dyslipidemia. (C) 2011 Elsevier Ireland Ltd. All rights reserved.