title: 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.
  
  
  CONCLUSIONS
  PPAR-δ and statin therapies have complementary effects in improving lipoprotein subfractions associated with atherogenic dyslipidemia.
authors.affiliation: Metabolex, Inc., 3876 Bay Center Place, Hayward, CA 94545, United States.
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Brian K
authors.initials: BK
authors.lastname: Roberts
authors.forename: Xueyan
authors.initials: X
authors.lastname: Wang
authors.forename: J Casey
authors.initials: JC
authors.lastname: Geaney
authors.forename: Sue
authors.initials: S
authors.lastname: Naim
authors.forename: Kathleen
authors.initials: K
authors.lastname: Wojnoonski
authors.forename: David B
authors.initials: DB
authors.lastname: Karpf
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
mesh_terms: D000085:Acetates / Q000627:therapeutic use*; D000704:Analysis of Variance; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D050177:Overweight / Q000150:complications; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D010316:Particle Size; D011758:Pyrroles / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: C572244:(2-methyl-4-(5-methyl-2-(4-trifluoromethyl-phenyl)-2H-(1,2,3)triazol-4-ylmethylsulfanyl)phenoxy)acetic acid; D000085:Acetates; D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D047495:PPAR gamma; D011758:Pyrroles; D014230:Triazoles; D000069059:Atorvastatin