title: PPARdelta in humans: genetic and pharmacological evidence for a significant metabolic function.
abstract: OBJECTIVE
  Abundant data in rodents suggest an important role for peroxisomal proliferators-activated receptor-delta (PPARdelta) in regulating skeletal muscle fatty acid oxidation and this has consequences for lipid and lipoprotein metabolism. Considerably less is known in humans and this review will focus on evidence derived from studies of the PPARD gene and pharmacological use of specific PPARdelta agonists.
  
  
  RESULTS
  Genetic association studies of single-nucleotide polymorphisms in the PPARD gene have only provided negative or conflicting evidence for gross phenotypes such as obesity, hyperlipidaemia and type 2 diabetes. This does not exclude more subtle effects in skeletal muscle metabolic function, but studies of this type need replication. A couple of recent studies using the specific PPARdelta agonist GW501516 suggest potent hypolipidaemic actions, presumably caused by enhanced fat oxidation in skeletal muscle.
  
  
  CONCLUSIONS
  Considering the hypolipidaemic effect in humans by PPARdelta agonists, long-term studies are needed to confirm efficacy and safety.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Nuffield Department of Clinical Medicine, University of Oxford, UK. Fredrik.Karpe@ocdem.ox.ac.uk
authors.forename: Fredrik
authors.initials: F
authors.lastname: Karpe
authors.forename: Ewa E
authors.initials: EE
authors.lastname: Ehrenborg
mesh_terms: D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D006951:Hyperlipoproteinemias / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D047494:PPAR delta / Q000819:agonists* / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D005227:Fatty Acids; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D047494:PPAR delta; D013844:Thiazoles