Therapeutic Potential of Peroxisome Proliferator-Activated Receptor Modulation in Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

A long neglected hepatic manifestation of the metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) arise as serious health burden with alarming global prevalence. The disease complex is currently attracting considerable interest of drug discovery and many experimental approaches are studied in all stages of clinical development. Peroxisome proliferator-activated receptors (PPARs) have a successful history as pharmaceutical targets in the treatment of several aspects of the metabolic syndrome and, therefore, a putative therapeutic value of PPAR modulators in NAFLD/NASH is obvious. However, so far only the PPARα/δ agonist elafibranor has revealed clear efficacy and reached an advanced stage of development while the far more established PPAR subtypes PPARα and PPARγ have disappointed. Still, clinical trial design and population might have obscured beneficial activities and, in addition, synergistic multi-target approaches as well as selective PPAR modulators could generate safer approaches with higher therapeutic efficacy.