Peroxisome Proliferator-Activated Receptors and Their Agonists in Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. In addition to the liver-related morbidity and mortality, NAFLD is now also associated with various extrahepatic diseases. Pathogenesis of NAFLD is multifactorial with limited pharmacotherapy options for the treatment of patients with NAFLD. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are involved in the transcriptional regulation of lipid metabolism, glucose homeostasis, energy balance, inflammation, and atherosclerosis. PPAR agonists are attractive options for treatment of NAFLD as they can act at multiple targets involved in the pathogenesis of NAFLD. We reviewed the available literature on the pathophysiological role of PPARs and use of PPAR agonists in the treatment of NAFLD. Original studies and review articles available on PubMed regarding the role of PPARs in the pathogenesis and utility of PPAR agonists in the treatment of NAFLD were included in this review article. ClinicalTrials.gov and Clinical Trials Registry-India sites were searched for ongoing studies on saroglitazar. The available literature suggests that PPARs play an important role in the pathogenesis of NAFLD. Use of PPAR gamma agonists is associated with histological improvement in NAFLD. Dual PPAR agonists with no or minimal PPAR gamma activity are being explored in the treatment of NAFLD. Because of the pathophysiological role of PPARs in NAFLD, PPAR agonists are attractive options for the treatment of patients with NAFLD. Dual PPAR agonists without significant gamma activity appear promising for the treatment of NAFLD.

Keywords: CPT-1, Carnitine palmitoyltransferase-1; MPC, mitochondrial pyruvate carrier; NAFLD, nonalcoholic fatty liver disease; NASH, Nonalcoholic steatohepatitis; NF-κB, nuclear factor-kappa beta; OR, odds ratio; PPAR, Peroxisome proliferator-activated receptors; RXR, retinoid X receptor; TZDs, thiazolidinediones; fatty liver; hepatic steatosis; metabolic syndrome; nonalcoholic steatohepatitis.