Perilipin 5 regulates hepatic stellate cell activation and high-fat diet-induced non-alcoholic fatty liver disease.

Autor: Yin X; Department of Internal Medicine, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Dong L; Department of Pediatrics, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Wang X; Department of Pediatrics, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Qin Z; Department of Internal Medicine, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Ma Y; Department of Internal Medicine, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Ke X; Department of Pediatrics, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Li Y; Department of Internal Medicine, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Wang Q; Department of Internal Medicine, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Mi Y; Department of Internal Medicine, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Lyu Q; Department of Clinical Nutrition, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Xu X; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Co-innovation Center of Henan Province for New drug R & D and Preclinical Safety, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China., Zheng P; Department of Internal Medicine, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Tang Y; Department of Internal Medicine, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.; Department of Pediatrics, Gastroenterology, Henan Key Laboratory of Rehabilitation Medicine, Henan Joint International Research Laboratory of Chronic Liver Injury and Henan Provincial Outstanding Overseas Scientists Chronic Liver Injury Studio, the Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Jazyk: angličtina
Zdroj: Animal models and experimental medicine [Animal Model Exp Med] 2024 Apr; Vol. 7 (2), pp. 166-178. Date of Electronic Publication: 2023 May 18.
DOI: 10.1002/ame2.12327
Abstrakt: Background: Nonalcoholic 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.
Methods: PLIN 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.
Results: Overexpression 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.
Conclusion: These findings highlight the unique regulatory role of PLIN 5 in HSCs and the role of PLIN 5 in the fibrosis process of NAFLD.
(© 2023 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)
Databáze: MEDLINE
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