• Logo
  • SBMUJournals

Effects of high fat medium condition on cellular gene expression profile: a network analysis approach

Hamid Asadzadeh-Aghdaei, Mohammad-Mehdi Zadeh-Esmaeel, Somayeh Esmaeili, Mostafa Rezaei –Tavirani, Sina Rezaei –Tavirani, Vahid Mansouri, Fatemeh Montazer




AIM: Evaluation of high fat medium (HFM) effect on gene expression profile human Sk-hep1 cells and determination of critical differential proteins are the aim of this study.

Background: There is correlation between high fat diet (HFD), obesity, and non-alcoholic fatty liver disease. Despite of wide range of investigations, molecular mechanism understanding of HFD of onset and progression of NAFLD implies more examination. In this study network analysis is applied to obtain a clear perspective about HFD effects and NAFLD. 

Methods: Gene expression profiles of human Sk-hep1 cells treated with HFM versus controls were extracted from GEO. Data was analyzed by GEO2R and the significant and characterized DEGs were included in the PPI network. Numbers of 10 top nodes of query DEGs based on four centrality parameters were selected to determine central nodes. The common hub nodes with at least other one central group were identified as central nodes. Action map was provided for the introduced central nodes.

Results: Heterogeneous nuclear ribonucleoprotein family including A1, A2/B1, D, R, and D-like, and five proteins (PRPF40A, SRSF1, PCF11, LSM8, and HSP90AA1) were introduced as differentially proteins.

Conclusion: mRNA processing and several biological terms including hypoxia and oxidative stress, apoptosis, regulation of cell morphology and cytoskeletal organization, and differentiation of micro tubes were introduced as dysregulated terms under HFM condition.



Liver, fat, network, gene


James OF, Day CP. Non-alcoholic steatohepatitis (NASH): a disease of emerging identity and importance. Journal of hepatology. 1998;29(3):495-501.

Zhu L, Baker SS, Gill C, Liu W, Alkhouri R, Baker RD, et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2013;57(2):601-9.

Yasutake K, Nakamuta M, Shima Y, Ohyama A, Masuda K, Haruta N, et al. Nutritional investigation of non-obese patients with non-alcoholic fatty liver disease: the significance of dietary cholesterol. Scandinavian journal of gastroenterology. 2009;44(4):471-7.

Takaki A, Kawai D, Yamamoto K. Molecular mechanisms and new treatment strategies for non-alcoholic steatohepatitis (NASH). International journal of molecular sciences. 2014;15(5):7352-79.

Vilar L, Oliveira CP, Faintuch J, Mello ES, Nogueira MA, Santos TE, et al. High-fat diet: a trigger of non-alcoholic steatohepatitis? Preliminary findings in obese subjects. Nutrition. 2008;24(11-12):1097-102.

Romestaing C, Piquet M-A, Bedu E, Rouleau V, Dautresme M, Hourmand-Ollivier I, et al. Long term highly saturated fat diet does not induce NASH in Wistar rats. Nutrition & metabolism. 2007;4(1):4.

Xu Z-J, Fan J-G, Ding X-D, Qiao L, Wang G-L. Characterization of high-fat, diet-induced, non-alcoholic steatohepatitis with fibrosis in rats. Digestive diseases and sciences. 2010;55(4):931-40.

Carmiel-Haggai M, Cederbaum AI, Nieto N. A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. The FASEB Journal. 2005;19(1):136-8.

Riordan JD, Nadeau JH. Modeling progressive non-alcoholic fatty liver disease in the laboratory mouse. Mammalian genome. 2014;25(9-10):473-86.

Karczewski KJ, Snyder MP. Integrative omics for health and disease. Nature Reviews Genetics. 2018;19(5):299.

Tavirani MR, Bashash D, Rostami FT, Tavirani SR, Nikzamir A, Tavirani MR, et al. Celiac disease microarray analysis based on system biology approach. Gastroenterology and Hepatology from bed to bench. 2018;11(3):216.

Abdollahi H, Azodi MZ, Hatami B. Protein interaction mapping interpretation of none alcoholic fatty liver disease model of rats after fat diet feeding. Gastroenterology and hepatology from bed to bench. 2017;10(Suppl1):S146.

Sarkar B, Lu J-Y, Schneider RJ. Nuclear import and export functions in the different isoforms of the AUF1/heterogeneous nuclear ribonucleoprotein protein family. Journal of Biological Chemistry. 2003;278(23):20700-7.

Oleksiewicz U, Liloglou T, Tasopoulou K-M, Daskoulidou N, Gosney JR, Field JK, et al. COL1A1, PRPF40A, and UCP2 correlate with hypoxia markers in non-small cell lung cancer. Journal of cancer research and clinical oncology. 2017;143(7):1133-41.

Thakur A, Bollig A, Wu J, Liao DJ. Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice. Molecular cancer. 2008;7(1):11.

Anczuków O, Rosenberg AZ, Akerman M, Das S, Zhan L, Karni R, et al. The splicing factor SRSF1 regulates apoptosis and proliferation to promote mammary epithelial cell transformation. Nature structural & molecular biology. 2012;19(2):220.

Das S, Anczuków O, Akerman M, Krainer AR. Oncogenic splicing factor SRSF1 is a critical transcriptional target of MYC. Cell reports. 2012;1(2):110-7.

Zou L, Zhang H, Du C, Liu X, Zhu S, Zhang W, et al. Correlation of SRSF1 and PRMT1 expression with clinical status of pediatric acute lymphoblastic leukemia. Journal of hematology & oncology. 2012;5(1):42.

Zhang Z, Fu J, Gilmour DS. CTD-dependent dismantling of the RNA polymerase II elongation complex by the pre-mRNA 3′-end processing factor, Pcf11. Genes & development. 2005;19(13):1572-80.

Liu Q, Liang X-h, Uliel S, Belahcen M, Unger R, Michaeli S. Identification and functional characterization of Lsm proteins in Trypanosoma brucei. Journal of Biological Chemistry. 2004;279(18):18210-9.

Zuehlke AD, Beebe K, Neckers L, Prince T. Regulation and function of the human HSP90AA1 gene. Gene. 2015;570(1):8-16.

Cai Y, Jogasuria A, Yin H, Xu M-J, Hu X, Wang J, et al. The detrimental role played by lipocalin-2 in alcoholic fatty liver in mice. The American journal of pathology. 2016;186(9):2417-28.

DOI: https://doi.org/10.22037/ghfbb.v12i0.1738