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BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases globally. Hepatic stellate cells (HSCs) are the major effector cells of liver fibrosis. HSCs contain abundant lipid droplets (LDs) in their cytoplasm during quiescence. Perilipin 5 (PLIN 5) is a LD surface‐associated protein that plays a crucial role in lipid homeostasis. However, little is known about the role of PLIN 5 in HSC activation.MethodsPLIN 5 was overexpressed in HSCs of Sprague–Dawley rats by lentivirus transfection. At the same time, PLIN 5 gene knockout mice were constructed and fed with a high‐fat diet (HFD) for 20 weeks to study the role of PLIN 5 in NAFLD. The corresponding reagent kits were used to measure TG, GSH, Caspase 3 activity, ATP level, and mitochondrial DNA copy number. Metabolomic analysis of mice liver tissue metabolism was performed based on UPLC‐MS/MS. AMPK, mitochondrial function, cell proliferation, and apoptosis‐related genes and proteins were detected by western blotting and qPCR.ResultsOverexpression of PLIN 5 in activated HSCs led to a decrease in ATP levels in mitochondria, inhibition of cell proliferation, and a significant increase in cell apoptosis through AMPK activation. In addition, compared with the HFD‐fed C57BL/6J mice, PLIN 5 knockout mice fed with HFD showed reduced liver fat deposition, decreased LD abundance and size, and reduced liver fibrosis.ConclusionThese findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is diffuse steatosis of hepatocytes and is the most common type of chronic liver disease. The benign and reversible stage of NAFLD is defined as simple fatty liver, which further progresses to non-alcoholic steatohepatitis (NASH), liver fibrosis, and even liver cancer. It is believed that in the future, NASH would be one of the primary reasons for advanced liver failure and the need for liver transplantation. NAFLD is considered to be closely related to genetics, environment, metabolic diseases, such as obesity and hyperlipidemia. From the macro-level of NAFLD understanding, this chapter systematically analyzes the research progress on the etiology, pathogenesis, diagnosis, treatment, and development trends of NAFLD.