Multifaceted roles of peroxisome proliferator-activated receptors (PPARs) at the cellular and whole organism levels

Chronic disorders, such as obesity, diabetes, inflammation, non-alcoholic fatty liver disease and atherosclerosis, are related to alterations in lipid and glucose metabolism, in which peroxisome proliferator-activated receptors (PPAR)alpha, PPAR beta/delta and PPAR gamma are involved. These receptors form a subgroup of ligand-activated transcription factors that belong to the nuclear hormone receptor family. This review discusses a selection of novel PPAR functions identified during the last few years. The PPARs regulate processes that are essential for the maintenance of pregnancy and embryonic development. Newly found hepatic functions of PPAR alpha are the mediation of female-specific gene repression and the protection of the liver from oestrogen induced toxicity. PPAR alpha also controls lipid catabolism and is the target of hypolipidaemic drugs, whereas PPAR gamma controls adipocyte differentiation and regulates lipid storage; it is the target for the insulin sensitising thiazolidinediones used to treat type 2 diabetes. Activation of PPAR beta/delta increases lipid catabolism in skeletal muscle, the heart and adipose tissue. In addition, PPAR beta/delta ligands prevent weight gain and suppress macrophage derived inflammation. In fact, therapeutic benefits of PPAR ligands have been confirmed in inflammatory and autoimmune diseases, such as encephalomyelitis and inflammatory bowel disease. Furthermore, PPARs promote skin wound repair. PPAR alpha favours skin healing during the inflammatory phase that follows injury, whilst PPAR beta/delta enhances keratinocyte survival and migration. Due to their collective functions in skin, PPARs represent a major research target for our understanding of many skin diseases. Taken altogether, these functions suggest that PPARs serve as physiological sensors in different stress situations and remain valuable targets for innovative therapies.