Peroxisome Proliferator Activated Receptor-δ

Adaptation to changes in energy balance is critical for survival of all organisms. Successful adaptation during mammalian evolution was driven by starvation, but energy excess leading to insulin resistance and atherosclerosis1 presents challenges for adaptation in the current era. The highly orchestrated response to nutritional status is mediated, in part, by peroxisome proliferator activated receptors (PPARs), which control lipid and glucose utilization as well as inflammatory responses in many tissues. The 3 members of the PPAR family, PPARα, PPARδ, and PPARγ, form heterodimers with the retinoid X receptor and bind to peroxisome proliferator response elements.2 PPAR expression patterns overlap, but PPARα is present in liver and muscle, PPARγ is mostly in adipocytes, PPARδ is present in many tissues, and all 3 are in macrophages.See accompanying article on page 52PPARδ, the least characterized family member, is induced in skeletal muscle after exercise.3 In mice, PPARδ activation increased muscle fatty acid oxidation and improved exercise tolerance.4 In healthy humans, a synthetic PPARδ agonist, GW501516, reduced postprandial plasma triglycerides, increased high-density lipoprotein, and increased muscle expression of enzymes involved in fatty acid oxidation.5 Similar effects were observed when PPARδ …