PPARs and nonalcoholic fatty liver disease

Area of Science:

• Hepatology
• Metabolic Diseases
• Molecular Endocrinology

Background:

• Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver conditions driven by metabolic dysfunction, increasing globally with obesity.
• NAFLD can advance to severe liver damage, including cirrhosis and hepatocellular carcinoma, necessitating effective treatments.
• Current management relies on lifestyle changes, which are challenging for sustained patient adherence, highlighting the need for pharmacological interventions.

Purpose of the Study:

• To review preclinical and clinical evidence on the therapeutic potential of peroxisome proliferator-activated receptor (PPAR) ligands for NAFLD.
• To assess the role of PPAR ligands in modulating key pathways involved in NAFLD pathogenesis.
• To provide an overview of the current research landscape for PPAR-based NAFLD therapies.

Main Methods:

• Systematic review of preclinical studies (in vitro and animal models) investigating PPAR ligand efficacy in NAFLD.
• Analysis of clinical trial data evaluating PPAR ligands in human NAFLD patients.
• Examination of the mechanisms of action of PPAR ligands on lipid and glucose metabolism relevant to NAFLD.

Main Results:

• Preclinical studies demonstrate that PPAR ligands can ameliorate steatosis, inflammation, and fibrosis in NAFLD models.
• Clinical studies suggest potential benefits of certain PPAR ligands in improving liver enzymes and metabolic parameters in NAFLD patients.
• PPAR ligands modulate gene expression involved in fatty acid oxidation, glucose homeostasis, and inflammation, key to NAFLD pathology.

Conclusions:

• PPAR ligands represent a promising therapeutic strategy for NAFLD, targeting fundamental metabolic pathways.
• Further clinical investigation is warranted to establish the safety and efficacy of specific PPAR ligands for NAFLD treatment.
• Targeting PPARs offers a potential pharmacological approach to manage the growing epidemic of NAFLD.