Triglyceride:high-density lipoprotein cholesterol effects in healthy subjects administered a peroxisome proliferator activated receptor delta agonist

  • Sprecher D
  • Massien C
  • Pearce G
 et al. 
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OBJECTIVE: Exercise increases fatty acid oxidation (FAO), improves serum high density lipoprotein cholesterol (HDLc) and triglycerides (TG), and upregulates skeletal muscle peroxisome proliferator activated receptor (PPAR)delta expression. In parallel, PPARdelta agonist-upregulated FAO would induce fatty-acid uptake (via peripheral lipolysis), and influence HDLc and TG-rich lipoprotein particle metabolism, as suggested in preclinical models. METHODS AND RESULTS: Healthy volunteers were allocated placebo (n=6) or PPARdelta agonist (GW501516) at 2.5 mg (n=9) or 10 mg (n=9), orally, once-daily for 2 weeks while hospitalized and sedentary. Standard lipid/lipoproteins were measured and in vivo fat feeding studies were conducted. Human skeletal muscle cells were treated with GW501516 in vitro and evaluated for lipid-related gene expression and FAO. Serum TG trended downwards (P=0.08, 10 mg), whereas TG clearance post fat-feeding improved with drug (P=0.02). HDLc was enhanced in both treatment groups (2.5 mg P=0.004, 10 mg P

Author-supplied keywords

  • ATP-Binding Cassette Transporters/genetics/metabol
  • Adult
  • Antigens, CD36/genetics/metabolism
  • Cells, Cultured
  • Fatty Acids/metabolism
  • Humans
  • Lipoproteins, HDL/*metabolism
  • Male
  • Muscle, Skeletal/cytology/drug effects/metabolism
  • Oxidation-Reduction/drug effects
  • PPAR delta/*agonists/genetics/metabolism
  • Thiazoles/*pharmacology
  • Triglycerides/*metabolism
  • Up-Regulation/drug effects

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  • D L Sprecher

  • C Massien

  • G Pearce

  • A N Billin

  • I Perlstein

  • T M Willson

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