The role of peroxisome proliferator-activated receptors in the pathogenesis of insulin resistance and septic shock

• Published in: Clinical and experimental health sciences (Online) 2015-01, Vol.5 (4), p.1
• Main Authors: Senol, Sefika, Tunctan, Bahar
• Format: Article
• Language: Turkish
• ISSN: 2146-3654; 2146-3654; 2459-1459
• DOI: 10.5455/musbed.20150715121617

Peroxisome proliferator-activated receptors are ligand-activated transcription factors and they belong to class II nuclear receptor family. To date, three subspecies have been identified: peroxisome proliferator-activated receptor (PPAR) ?, PPARß and PPAR?. PPAR? is mainly involved in the regulation of lipid metabolism and inflammatory processes. Since PPARß is expressed in almost all tissues, the functional identity of it is not yet clear. PPAR? plays a key role in glucose homeostasis and the regulation of adipogenesis. Insulin resistance is attenuated biological response despite circulating normal or high levels of insulin in blood. In insulin resistance, the response caused by insulin isn't sufficient or adequate at all tissues particularly in muscle, fat and liver. Development of insulin resistance is prevented by PPAR? through regulation of genes affecting lipid metabolism and by PPAR? through provision of glucose homeostasis by different mechanisms. Sepsis is a systemic inflammatory response against a manifest or a potential infection; and septic shock is the severe form of sepsis that is accompanied by hypotension unresponsive to intravenous fluid administration. In preclinical studies proinflammatory gene expression was prevented by the inhibition of activation of transcription factors such as nuclear factor ?B and activator protein-1 which are involved in the pathogenesis of sepsis and septic shock by PPAR agonists. This review focuses on the role of PPARs in the pathogenesis of insulin resistance and septic shock and discusses the potential therapeutic benefits of PPAR agonists.