Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, frequently associated with obesity and type 2 diabetes. Steatosis is the initial stage of the disease, which is characterized by lipid accumulation in hepatocytes, which can progress to non-alcoholic steatohepatitis (NASH) with inflammation and various levels of fibrosis that further increase the risk of developing cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is influenced by interactions between genetic and environmental factors and involves several biological processes in multiple organs. No effective therapy is currently available for the treatment of NAFLD. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that regulate many functions that are disturbed in NAFLD, including glucose and lipid metabolism, as well as inflammation. Thus, they represent relevant clinical targets for NAFLD. In this review, we describe the determinants and mechanisms underlying the pathogenesis of NAFLD, its progression and complications, as well as the current therapeutic strategies that are employed. We also focus on the complementary and distinct roles of PPAR isotypes in many biological processes and on the effects of first-generation PPAR agonists. Finally, we review novel and safe PPAR agonists with improved efficacy and their potential use in the treatment of NAFLD.
Highlights
The aim of this review is to provide information for a better understanding of the factors that impact the development, progression and complications of liver steatosis, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
We discuss the roles of the nuclear receptors peroxisome proliferator-activated receptors (PPARs) in the regulation of biological processes that are participating in NAFLD, which include energy metabolism, inflammation, and fibrosis
Hepatic steatosis in the absence of excessive alcohol consumption is the hallmark of NAFLD, which is characterized by abnormal accumulation of triglycerides (TGs) in hepatocytes, a condition called non-alcoholic fatty liver (NAFL)
Summary
The aim of this review is to provide information for a better understanding of the factors that impact the development, progression and complications of liver steatosis, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). We discuss the roles of the nuclear receptors peroxisome proliferator-activated receptors (PPARs) in the regulation of biological processes that are participating in NAFLD, which include energy metabolism, inflammation, and fibrosis. PPARs are ligand activated transcription factors; we present new agonists that are currently in clinical trials for their potential to treat NAFLD for which no effective therapy is available
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