PPARδ in humans: genetic and pharmacological evidence for a significant metabolic function

Purpose of review Abundant data in rodents suggest an important role for peroxisomal proliferators-activated receptor-delta (PPAR delta) 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 PPAR delta agonists. Recent findings 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 PPAR delta agonist GW501516 suggest potent hypolipidaemic actions, presumably caused by enhanced fat oxidation in skeletal muscle. Summary Considering the hypolipidaemic effect in humans by PPAR delta agonists, long-term studies are needed to confirm efficacy and safety.