Mechanisms of cholesterol metabolism imbalance in a PA-induced non-alcoholic fatty liver disease cell model
10.11665/j.issn.1000-5048.2023032401
- VernacularTitle:非酒精性脂肪性肝病细胞模型中胆固醇代谢紊乱机制
- Author:
Yuting ZHANG
1
;
Anhui WANG
;
Jinni YANG
;
Jiachun LIN
;
Yuan TIAN
;
Haijuan DONG
;
Zunjian ZHANG
;
Rui SONG
Author Information
1. 中国药科大学药物质量与安全预警教育部重点实验室
- Publication Type:Journal Article
- Keywords:
non-alcoholic fatty liver disease(NAFLD);
cholesterol metabolism;
oxysterols;
bile acids;
STARD1
- From:
Journal of China Pharmaceutical University
2023;54(4):490-500
- CountryChina
- Language:Chinese
-
Abstract:
Liver cholesterol metabolism disorder plays an important role in the development of non-alcoholic fatty liver disease (NAFLD).In order to reveal the molecular mechanism of cholesterol homeostasis imbalance induced by saturated fatty acids, HepG2 cells were stimulated with palmitic acid (PA).Lipids accumulation was analyzed by Oil Red O staining, intracellular triglyceride and cholesterol quantification.The level of genes and proteins related to cholesterol homeostasis was measured by RT-qPCR and western blotting.Additionally, intracellular bile acids and mitochondrial oxysterols were detected by LC-MS/MS.The results demonstrated that intracellular lipids such as TG and TC were significantly increased in the model with PA stimulation.Although no significant difference was detected in genes related to cholesterol synthesis and uptake, the protein expression of ABCG5 and LXRα were significantly down-regulated, indicating a decrease in cholesterol efflux.Meanwhile, the gene expression of STARD1 and CYP7B1, which are responsible for bile acid alternative synthesis, were markedly enhanced, along with a significant increase of cholesterol and 27-OHC in mitochondria and CDCA in cells.These results suggested that PA overload may disrupt cholesterol homeostasis by inhibiting cholesterol efflux and promoting bile acids synthesis.
