Mechanisms of cholesterol metabolism imbalance in a PA-induced non-alcoholic fatty liver disease cell model

ZHANG Yuting; WANG Anhui; YANG Jinni; LIN Jiachun; TIAN Yuan; DONG Haijuan; ZHANG Zunjian; SONG Rui

doi:10.11665/j.issn.1000-5048.2023032401

Journal of China Pharmaceutical University > 2023 > 54(4): 490-500. > DOI: 10.11665/j.issn.1000-5048.2023032401

ZHANG Yuting, WANG Anhui, YANG Jinni, LIN Jiachun, TIAN Yuan, DONG Haijuan, ZHANG Zunjian, SONG Rui. Mechanisms of cholesterol metabolism imbalance in a PA-induced non-alcoholic fatty liver disease cell model[J]. Journal of China Pharmaceutical University, 2023, 54(4): 490-500. DOI: 10.11665/j.issn.1000-5048.2023032401

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Mechanisms of cholesterol metabolism imbalance in a PA-induced non-alcoholic fatty liver disease cell model

1.
Key Laboratory of Drug Quality Control & Pharmacovigilance, China Pharmaceutical University, Ministry of Educational, Nanjing 210009
2.
The Public Laboratory Platform of China Pharmaceutical University, Nanjing 210009, China

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Received Date: March 23, 2023
Revised Date: July 10, 2023

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Abstract

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.
- non-alcoholic fatty liver disease(NAFLD),
- cholesterol metabolism,
- oxysterols,
- bile acids,
- STARD1

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References

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