Transcriptomic profiling and analysis of key regulatory molecules in non-alcoholic fatty liver disease

Chinese Hepatolgy ›› 2023, Vol. 28 ›› Issue (12): 1466-1471.

• Non-alcoholic Fatty Liver Disease • Previous Articles Next Articles

Transcriptomic profiling and analysis of key regulatory molecules in non-alcoholic fatty liver disease

CHENG Niang-mei^1,2, LIU Ke-xin^1,2, WANG Ying-chao^1,2, CHEN Ming-sheng¹

1. Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, China;
2. The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Med-X Center, Fuzhou University, Fuzhou 350116, China

Received:2023-07-18 Online:2023-12-31 Published:2024-03-01
Contact: CHEN Ming-sheng, Email: cmscms@fjmu.edu.cn

Abstract

Abstract: Objective To explore the differentially expressed genes in Non-alcoholic fatty liver disease (NAFLD) compared to normal liver cells, aiming to elucidate genetic varations contributing to the pathophysiology of NAFLD.Methods Establishing the NAFLD cell model: Human normal liver cells(LO2) were treated with palmitic acid to induce NAFLD characteristics. Subsequently, Oil red O staining was employed to assess cellular fat accumulation, and flow cytometry was utilized to evaluate the apoptotic effects of palmitic acid on LO2 cells. Transcriptome sequencing was performed on both normal LO2 cells and cells in the induced model to identify differentially expressed genes. These genes underwent KEGG and GO functional enrichment analysis. Additionally, the expression levels of these differential genes were quantified using RT-PCR.Results Increasing concentrations of palmitic acid led to more pronounced cellular fat accumulation. Considering this alongside the apoptosis rate, an optimal concentration of palmitic acid was selected for further study. Transcriptomic analysis revealed that, in the model group, there were 780 differentially expressed genes compared to the control group, with 447 genes upregulated and 333 downregulated. GO enrichment analysis demonstrated significant pathway involvement, and KEGG pathway analysis indicated major involvement in 20 signaling pathways, including TNF, protein export, and NOD signaling pathways. RT-PCR results showed that FGF21, AMBP, GOLGA7B, and DDIT3 were highly expressed in the NAFLD model, whereas SPTLC3, PALM2, and SPTSBB showed low expression.Conclusion NAFLD is observed to induce the expression of specific differential genes, potentially regulating the progression of NAFLD through key target genes involved in lipid metabolism.

Key words: NAFLD, Palmitic acid, LO2, Transcriptome sequencing

CHENG Niang-mei, LIU Ke-xin, WANG Ying-chao, CHEN Ming-sheng. Transcriptomic profiling and analysis of key regulatory molecules in non-alcoholic fatty liver disease[J]. Chinese Hepatolgy, 2023, 28(12): 1466-1471.

References

[1] Younossi ZM, Golabi P, De avila L, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis[J]. J Hepatol, 2019, 71(4): 793-801.
[2] Arab JP, Candia R, Zapata R, et al. Management of nonalcoholic fatty liver disease: an evidence-based clinical practice review[J]. World J Gastroenterol, 2014, 20(34): 12182-12201.
[3] Cobbina E, Akhlaghi F. Non-alcoholic fatty liver disease (NAFLD) - pathogenesis, classification, and effect on drug metabolizing enzymes and transporters[J]. Drug Metab Rev, 2017, 49(2): 197-211.
[4] Friedman SL, Neuschwander-tetri BA, Rinella M, et al. Mechanisms of NAFLD development and therapeutic strategies[J]. Nat Med, 2018, 24(7): 908-922.
[5] Pouwels S, Sakran N, Graham Y, et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss[J]. BMC Endocr Disord, 2022, 22(1): 63.
[6] Younossi Z, Tacke F, Arrese M, et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Hepatology, 2019, 69(6): 2672-2682.
[7] Ferguson D, Finck BN. Emerging therapeutic approaches for the treatment of NAFLD and type 2 diabetes mellitus[J]. Nat Rev Endocrinol, 2021, 17(8): 484-495.
[8] Inagaki T. Research perspectives on the regulation and physiological Functions of FGF21 and its association with NAFLD[J]. Front Endocrinol (Lausanne), 2015, 6: 147.
[9] Angelin B, Larsson TE, Rudling M. Circulating fibroblast growth factors as metabolic regulators--a critical appraisal[J]. Cell Metab, 2012, 16(6): 693-705.
[10] Li H, Fang Q, Gao F, et al. Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride[J]. J Hepatol, 2010, 53(5): 934-940.
[11] Yong J, Parekh VS, Reilly SM, et al. Chop/Ddit3 depletion in beta cells alleviates ER stress and corrects hepatic steatosis in mice[J]. Sci Transl Med, 2021, 13(604).
[12] Igci M, Arslan A, Igci YZ, et al. Bikunin and alpha1-microglobulin/bikunin precursor (AMBP) gene mutational screening in patients with kidney stones: a case-control study[J]. Scand J Urol Nephrol, 2010, 44(6): 413-419.
[13] Yoon SY, Kim JM, Oh JH, et al. Gene expression profiling of human HBV- and/or HCV-associated hepatocellular carcinoma cells using expressed sequence tags[J]. Int J Oncol, 2006, 29(2): 315-327.
[14] Ijuin S, Oda K, Mawatari S, et al. Serine palmitoyltransferase long chain subunit 3 is associated with hepatocellular carcinoma in patients with NAFLD[J]. Mol Clin Oncol, 2022, 16(2): 55.
[15] Xu L, Xiao T, Xu L, et al. Identification of therapeutic targets and prognostic biomarkers in cholangiocarcinoma via WGCNA[J]. Front Oncol, 2022, 12: 977992.

Transcriptomic profiling and analysis of key regulatory molecules in non-alcoholic fatty liver disease

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 4

Recommended Articles

Metrics

Comments

[1]	LIU Lu, ZHU Jin-zhou, LIU Xiao-lin, WANG Chao, YI Min-yuen, GAO Jing-wen, XU Chun-fang. Development of Prediction Models Based on Machine Learning for Non-alcoholic fatty liver disease [J]. Chinese Hepatolgy, 2023, 28(4): 469-473.
[2]	GAO Lan, LIU Hai-wei, LIN Lu, CHEN Kai-ning. Effect of Liraglutide on ERS in T2DM and NAFLD patients and its clinic efficacy [J]. Chinese Hepatolgy, 2020, 25(9): 972-974.
[3]	LI Wen-song, CHEN Li-yan, BI Man-ru, YAN Bing-zhu, KANG Lan, YANG Peng-fei, WANG Xiao-ren, YANG Bao-shan.. The effects of ghrelin on hepatic oxidative stress and Akt/GSK3β signaling pathway in high-fat diet-fed rats [J]. Chinese Hepatolgy, 2017, 22(7): 597-601.
[4]	XIE Lan-feng, SHEN Ting-ting, ZHENG Ce, WANG Pi-xiao, WEI Qiao-fang, YANG Chang-qing, ZHANG Qin. Role of DKK3 in non-alcoholic fatty liver disease of mice model [J]. Chinese Hepatolgy, 2017, 22(5): 414-417.