Although activation of peroxisome proliferator activated receptor (PPAR) g and a has produced many clinical benefits in patients with diabetes (PPARg) and hypertriglyceridemia (PPARa), little is known about the effects of PPARd activation, especially in humans. To examine this issue, Risérius et al. performed a double-blind, randomized, three-parallel group, 2-week study in moderately obese men. The first group was put on placebo, the second group on PPARa agonist GW590735, and the third group on PPARd agonist GW501516. Men treated with the PPARd agonist had significant improvements in circulating triglycerides (-30%), apolipoprotein B (-26%), LDL cholesterol (-23%), and insulin (-11%) levels, whereas no changes were observed in HDL cholesterol levels. Urinary isoprostanes also dropped by 30%. Liver fat content decreased as a result of changes in triglyceride levels. Muscle biopsies showed that the pattern of expression of specific genes involved in fatty acid handling also improved in men treated with the PPARd agonist. The authors concluded that the metabolic benefits observed with PPARd activation were likely due to increased muscle fatty acid oxidation and that a larger study is warranted to further evaluate the clinical efficacy of PPARd agonists.
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