PPARδ: A dagger in the heart of the metabolic syndrome

Obesity is a growing threat to global health by virtue of its association with insulin resistance, glucose intolerance, hypertension, and dyslipidemia, collectively known as the metabolic syndrome or syndrome X. The nuclear receptors PPARα and PPARγ are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively, and drugs that modulate these receptors are currently in clinical use. More recent work on the less-described PPAR isotype PPARδ has uncovered a dual benefit for both hypertriglyceridemia and insulin resistance, highlighting the broad potential of PPARδ in the treatment of metabolic disease. PPARδ enhances fatty acid catabolism and energy uncoupling in adipose tissue and muscle, and it suppresses macrophage-derived inflammation. Its combined activities in these and other tissues make it a multifaceted therapeutic target for the metabolic syndrome with the potential to control weight gain, enhance physical endurance, improve insulin sensitivity, and ameliorate atherosclerosis.