Emerging roles of PPARδ in metabolism

PPARδ differs from the other two PPAR isotypes (α and γ) by its more wide-spread tissue-specific expression pattern, its involvement in developmental processes and its profound impact on muscle and heart fat metabolism. Activation of PPARδ modulates inflammatory responses of macrophages and is linked to altered lipoprotein metabolism, most importantly a significant raise of HDL cholesterol. PPARδ activation in the liver decreases hepatic glucose output, thereby contributing to improved glucose tolerance and insulin sensitivity. Several studies have shown that PPARδ polymorphisms are associated with plasma lipid levels, body mass index and the risk for diabetes and coronary heart disease. These findings support that high affinity PPARδ agonists may be promising drugs of the future to treat the metabolic syndrome which is an expanding overweight-related health threat characterized by insulin resistance, hyperglycemia, dyslipidemia, hypertension, and accelerated atherosclerosis.