The Nuclear Hormone Receptor PPAR gamma as a Therapeutic Target in Major Diseases

The peroxisome proliferator-activated receptor gamma (PPAR gamma) belongs to the nuclear hormone receptor superfamily and regulates gene expression upon heterodimerization with the retinoid X receptor by ligating to peroxisome proliferator response elements (PPREs) in the promoter region of target genes. Originally, PPAR gamma was identified as being essential for glucose metabolism. Thus, synthetic PPAR gamma agonists, the thiazolidinediones (TZDs), are used in type 2 diabetes therapy as insulin sensitizers. More recent evidence implied an important role for the nuclear hormone receptor PPAR gamma in controlling various diseases based on its anti-inflammatory, cell cycle arresting, and proapoptotic properties. In this regard, expression of PPAR gamma is not restricted to adipocytes, but is also found in immune cells, such as B and T lymphocytes, monocytes, macrophages, dendritic cells, and granulocytes. The expression of PPAR gamma in lymphoid organs and its modulation of macrophage inflammatory responses, lymphocyte proliferation, cytokine production, and apoptosis underscore its immune regulating functions. Moreover, PPAR gamma expression is found in tumor cells, where its activation facilitates antitumorigenic actions. This review provides an overview about the role of PPAR gamma as a possible therapeutic target approaching major, severe diseases, such as sepsis, cancer, and atherosclerosis.