Experimental model and novel therapeutic targets for non-alcoholic fatty liver disease development

Experimental model and novel therapeutic targets for non-alcoholic fatty liver disease development

Non-alcoholic fatty liver disease (NAFLD) is a complex disorder characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption. It is one of the most common liver diseases worldwide, affecting approximately 25% of the global population. It is closely associated with obesity, type 2 diabetes, and metabolic syndrome. Moreover, NAFLD can progress to non-alcoholic steatohepatitis, which can cause liver cirrhosis, liver failure, and hepatocellular carcinoma. Currently, there are no approved drugs for the treatment of NAFLD. Therefore, the development of effective drugs is essential for NAFLD treatment. In this article, we discuss the experimental models and novel therapeutic targets for NAFLD. Additionally, we propose new strategies for the development of drugs for NAFLD. INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is a metabolic syndrome in chronic liver disease, affecting > 25% of the adult population worldwide [1]. Obesity is a major cause of NAFLD and other metabolic diseases [2]. Various factors contribute to NAFLD development, with obesity and type 2 diabetes mellitus (T2DM) being the most potent factors leading to NAFLD via dysregulation of glucose metabolism and insulin resistance (IR) [3]. Dysfunction in glucose uptake, IR, and hyperlipidemia can induce hepatocellular apoptosis by triggering inflammation or disrupting cellular homeostasis [4]. Although various drugs have been developed to target inflammation, oxidative stress, lipid accumulation, and IR, they exert adverse side effects in patients with NAFLD [5]. Liver disease progression involves hepatic steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC) [4]. NAFLD pathogenesis can be explained by the “multiple-hit theory,” which elucidates the progression from normal