Abstract
Metabolic syndrome is estimated to affect more than one in five adults, and its prevalence is growing in the adult and pediatric populations. The most widely recognized metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a proinflammatory state as well. Peroxisome proliferator-activated receptors (PPARs) may serve as potential therapeutic targets for treating the metabolic syndrome and its related risk factors. The PPARs are transcriptional factors belonging to the ligand-activated nuclear receptor superfamily. So far, three isoforms of PPARs have been identified, namely, PPAR-α, PPAR-β/δ, and PPAR-γ. Various endogenous and exogenous ligands of PPARs have been identified. PPAR-α and PPAR-γ are mainly involved in regulating lipid metabolism, insulin sensitivity, and glucose homeostasis, and their agonists are used in the treatment of hyperlipidemia and T2DM. Whereas PPAR-β/δ function is to regulate lipid metabolism, glucose homeostasis, anti-inflammation, and fatty acid oxidation and its agonists are used in the treatment of metabolic syndrome and cardiovascular diseases. This review mainly focuses on the biological role of PPARs in gene regulation and metabolic diseases, with particular focus on the therapeutic potential of PPAR modulators in the treatment of thrombosis.
Highlights
According to World Health Organization global status reports, 80% of the 347 million people with diabetes globally will die of cardiovascular disease [1], and it will be the 7th leading cause of death in 2030 [2]
During the last decade it has been extensively demonstrated that risk factors of metabolic syndrome often associated with obesity, characterized by macrophage infiltration and activation in adipose tissue and liver can be treated by PPARS targets [18]
peroxisome proliferator-activated receptors (PPARs)-α belongs to the nuclear receptor superfamily and was the first to be identified as PPAR receptor
Summary
According to World Health Organization global status reports, 80% of the 347 million people with diabetes globally will die of cardiovascular disease [1], and it will be the 7th leading cause of death in 2030 [2]. Peroxisome proliferator-activated receptor (PPAR) is a subfamily of nuclear hormone receptors [6,7,8], that function as ligand-activated transcription factors to regulate various biological processes. All PPAR isoforms function mainly as transcription factors [12] They control and regulate the expression of large number of genes involved in regulating the intermediary metabolism of glucose and lipids, homeostasis, adipogenesis, insulin sensitivity, immune response, cell growth, and differentiation [6, 12,13,14,15]. During the last decade it has been extensively demonstrated that risk factors of metabolic syndrome often associated with obesity, characterized by macrophage infiltration and activation in adipose tissue and liver can be treated by PPARS targets [18]. The binding of PPAR with p65 will prevent completion of signaling through the NF-κB pathway, and binding with c-jun will interfere with AP-1 signaling pathway
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