Key result
PPARdelta agonists suggest potent hypolipidaemic actions despite conflicting genetic evidence for metabolic phenotypes.
Why the study?
Considerably less is known about the metabolic role of PPARdelta in humans compared to rodents, particularly regarding genetic and pharmacological evidence.
PPARdelta agonists show potential for potent hypolipidaemic actions in humans, though long-term efficacy and safety data are still needed.
Potential hypolipidaemic effects of PPARdelta agonists merit trials; leaves open PPARD variant contributions to metabolic risk.
PURPOSE OF REVIEW: 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. 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 PPARdelta agonist GW501516 suggest potent hypolipidaemic actions, presumably caused by enhanced fat oxidation in skeletal muscle. SUMMARY: Considering the hypolipidaemic effect in humans by PPARdelta agonists, long-term studies are needed to confirm efficacy and safety.
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Karpe et al. (2009) conducted a review in Obesity, hyperlipidaemia, and type 2 diabetes. PPARdelta agonists (e.g., GW501516) and PPARD gene polymorphisms was evaluated on Metabolic phenotypes and lipid levels. PPARdelta agonists such as GW501516 suggest potent hypolipidaemic actions in humans, whereas genetic association studies of PPARD polymorphisms provide conflicting evidence for metabolic phenotypes.
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