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

Abstract

OBJECTIVE:

Determine the effects of treatment with a selective PPAR-δ 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-δ 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 ∼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-δ and statin therapies have complementary effects in improving lipoprotein subfractions associated with atherogenic dyslipidemia.

• Authors: Yun-Jung Choi, Brian K Roberts, Xueyan Wang, J Casey Geaney, Sue Naim, Kathleen Wojnoonski, David B Karpf, Ronald M Krauss
• Journal: Atherosclerosis (Atherosclerosis) Vol. 220 Issue 2 Pg. 470-6 (Feb 2012) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 22169113 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• (2-methyl-4-(5-methyl-2-(4-trifluoromethyl-phenyl)-2H-(1,2,3)triazol-4-ylmethylsulfanyl)phenoxy)acetic acid
• Acetates
• Biomarkers
• Heptanoic Acids
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Hypolipidemic Agents
• Lipoproteins
• PPAR gamma
• Pyrroles
• Triazoles
• Atorvastatin

Topics

• Acetates (therapeutic use)
• Analysis of Variance
• Atherosclerosis (blood, drug therapy, etiology)
• Atorvastatin
• Biomarkers (blood)
• Chi-Square Distribution
• Double-Blind Method
• Drug Therapy, Combination
• Dyslipidemias (blood, complications, drug therapy)
• Female
• Heptanoic Acids (therapeutic use)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Hypolipidemic Agents (therapeutic use)
• Lipoproteins (blood)
• Male
• Middle Aged
• Obesity (complications)
• Overweight (complications)
• PPAR gamma (agonists, metabolism)
• Particle Size
• Pyrroles (therapeutic use)
• Time Factors
• Treatment Outcome
• Triazoles (therapeutic use)