Non-Alcoholic Fatty Liver Disease: Translating Disease Mechanisms into Therapeutics Using Animal Models

• Published in: International journal of molecular sciences 2023-06, Vol.24 (12), p.9996
• Main Authors: Basha, Amina, May, Sarah C, Anderson, Ryan M, Samala, Niharika, Mirmira, Raghavendra G
• Format: Article
• Language: English
• Subjects: Adipocytes; Analysis; Animal models; Animals; Body fat; Carbohydrates; Carcinoma, Hepatocellular - metabolism; Cholesterol; Cirrhosis; Diabetes; Diet; Disease Models, Animal; Endoplasmic reticulum; ER stress; Fatty acids; Fatty liver; Genetic engineering; Glucose; Hepatocellular carcinoma; Homeostasis; Inflammation; Insulin resistance; Lipids; Liver; Liver - metabolism; Liver cirrhosis; Liver Cirrhosis - metabolism; Liver diseases; Liver Neoplasms - metabolism; Medical research; Medicine, Experimental; Metabolism; Molecular modelling; Musculoskeletal system; Mutation; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - metabolism; nutrition; Obesity; Oxidation resistance; Oxidative stress; Pathogenesis; Pathophysiology; Review; Trans fats; Triglycerides; Type 2 diabetes
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24129996

Nonalcoholic fatty liver disease (NAFLD) is a range of pathologies arising from fat accumulation in the liver in the absence of excess alcohol use or other causes of liver disease. Its complications include cirrhosis and liver failure, hepatocellular carcinoma, and eventual death. NAFLD is the most common cause of liver disease globally and is estimated to affect nearly one-third of individuals in the United States. Despite knowledge that the incidence and prevalence of NAFLD are increasing, the pathophysiology of the disease and its progression to cirrhosis remain insufficiently understood. The molecular pathogenesis of NAFLD involves insulin resistance, inflammation, oxidative stress, and endoplasmic reticulum stress. Better insight into these molecular pathways would allow for therapies that target specific stages of NAFLD. Preclinical animal models have aided in defining these mechanisms and have served as platforms for screening and testing of potential therapeutic approaches. In this review, we will discuss the cellular and molecular mechanisms thought to contribute to NAFLD, with a focus on the role of animal models in elucidating these mechanisms and in developing therapies.