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Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor found predominantly in the liver that is involved in the regulation of lipid homeostasis. Activation of PPARα results in expression of a variety of genes, particularly those involved in fatty acid β-oxidation, binding, and transport. GW 9578 is a potent agonist of PPARα that activates the murine and human receptors with EC50 values of 0.005 and 0.05 μM, respectively. GW 9578 is highly selective for PPARα compared to PPARγ and PPARδ, which it activates in murine at EC50 values of 0.15 and 2.6 μM, respectively and in human at 1.0 and 1.4 μM, respectively. GW 9578 is a potent lipid lowering agent that may reduce insulin resistance. When 0.2 mg/kg GW 9578 was given orally once daily for three days, serum total LDL cholesterol was decreased 40-60% in male Sprague-Dawely rats. Obese Zucker rats treated with 5 mg/kg GW 9578 for nine days had markedly reduced serum insulin concentrations compared to controls.

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