ABSTRACT
This chapter aims at comprehensively summarizing the current knowledge on the pleiotropic roles of peroxisome proliferator-activated receptors (PPARs) in the pathophysiology of nonalcoholic steatohepatitis (NASH) viewed as an integrated part of metabolic and cardiovascular derangements, which must serve as a rationale for their use in the treatment of this condition. The panPPAR agonist lanifibranor was generally well-tolerated with a low dropout rate for adverse events. Mice with a PPARa mutant that only has transrepressive activity are protected against the development of NASH but not steatosis, while mice with wild-type PPARa are protected from both NASH and steatosis. PPARa also has anti-inflammatory properties, mainly by transrepression of pro-inflammatory target genes. Due to their key role in the transcriptional regulation of glucose and lipid metabolism, PPAR ligands hold promise as therapeutic agents for NAFLD. PPARS are key regulators of many of the adversely affected mechanistic pathways.
