The role of PPARβ/δ in the management of metabolic syndrome and its associated cardiovascular complications.

The association between metabolic syndrome and cardiovascular diseases raises important questions about the underlying pathological processes, especially for designing targeted therapeutic interventions. The Peroxisome Proliferators Activated Receptors (PPARs) are ligand-activated transcription factors that control lipid and glucose metabolism. Accumulating data suggest that PPARs may serve as potential targets for treating metabolic diseases and their cardiovascular complications. PPARs regulate gene expression by binding with RXR as a heterodimeric partner to specific DNA sequences, termed PPAR response elements. In addition, PPARs may modulate gene transcription also by directly interfering with other transcription factor pathways in a DNA-binding independent manner. To date, three different PPAR isoforms, designated α, β/δ and γ, have been identified. PPARα and PPARγ are the most extensively examined and characterized, mainly because they are activated by compounds, such as fibrates and thiazolidinediones, that are in clinical use for the treatment of hypertriglyceridemia and insulin resistance, respectively. In contrast the role of PPARβ/δ in metabolism has been less investigated. The recent availability of specific PPARβ/δ agonists revealed that PPARβ/δ plays a crucial role in fatty acid metabolism in several tissues. Besides, PPARβ/δ activation exerts beneficial effects against organ-related ischemic events, such as myocardial and cerebral infarction, which are among the most critical cardiovascular complications evoked by metabolic dysregulation. This paper reviews the evidence and recent developments relating to the potential therapeutic effects of PPARβ/δ agonists in the treatment of metabolic syndrome and its associated cardiovascular risk factors.