Role of peroxisome proliferator-activated receptors in non-alcoholic fatty liver disease inflammation

Overweight and obesity have been identified as the most important risk factors for many diseases, including cardiovascular disease, type 2 diabetes and lipid disorders, such as non-alcoholic fatty liver disease (NAFLD). The metabolic changes associated with obesity are grouped to define metabolic syndrome, which is one of the main causes of morbidity and mortality in industrialized countries. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is one of the most prevalent liver diseases worldwide. Inflammation plays an important role in the development of numerous liver diseases, contributing to the progression to more severe stages, such as non-alcoholic steatohepatitis and hepatocellular carcinoma. Peroxisome proliferator-activated receptors (PPARs) are binder-activated nuclear receptors that are involved in the transcriptional regulation of lipid metabolism, energy balance, inflammation and atherosclerosis. Three isotypes are known: PPAR-alpha, PPAR delta/beta and PPAR-gamma. These isotypes play different roles in diverse tissues and cells, including the inflammatory process. In this review, we discuss current knowledge on the role PPARs in the hepatic inflammatory process involved in NAFLD as well as new pharmacological strategies that target PPARs.