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Fabp5 is a Common Gene Between a High-cholesterol Diet and Acute Pancreatitis

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Journal Front Nutr
Date 2024 Jan 8
PMID 38188879
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Abstract

Background And Aims: Hypercholesterolemia has been identified as risk factor for severe acute pancreatitis (AP). We aimed to identify the common differentially expressed genes (DEGs) between a high-cholesterol diet and AP.

Methods: We retrived gene expression profiles from the GEO database. DEGs were assessed using GEO2R. For AP hub genes, we conducted functional enrichment analysis and protein-protein interaction (PPI) analysis. GeneMANIA and correlation analysis were employed to predict potential DEG mechanisms. Validation was done across various healthy human tissues, pancreatic adenocarcinoma, peripheral blood in AP patients, and Sprague-Dawley rats with AP.

Results: The gene "Fabp5" emerged as the sole common DEG shared by a high-cholesterol diet and AP. Using the 12 topological analysis methods in PPI network analysis, Rela, Actb, Cdh1, and Vcl were identified as hub DEGs. GeneMANIA revealed 77.6% physical interactions among Fabp5, TLR4, and Rela, while genetic correlation analysis indicated moderate associations among them. Peripheral blood analysis yielded area under the ROC curve (AUC) values of 0.71, 0.63, 0.74, 0.64, and 0.91 for Fabp5, TLR4, Actb, Cdh1 genes, and artificial neural network (ANN) model respectively, in predicting severe AP. immunohistochemical analysis demonstrated higher Fabp5 expression in the hyperlipidemia-associated AP group compared to the AP and control groups.

Conclusion: Fabp5 emerged as the common DEG connecting a high-cholesterol diet and AP. Rela was highlighted as a crucial hub gene in AP. Genetic interactions were observed among Fabp5, TLR4, and Rela. An ANN model consisting of Fabp5, TLR4, Actb, and Cdh1 was helpful in predicting severe AP.

References
1.
Lumeng C, Bodzin J, Saltiel A . Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007; 117(1):175-84. PMC: 1716210. DOI: 10.1172/JCI29881. View

2.
Fan L, Hui X, Mao Y, Zhou J . Identification of Acute Pancreatitis-Related Genes and Pathways by Integrated Bioinformatics Analysis. Dig Dis Sci. 2019; 65(6):1720-1732. DOI: 10.1007/s10620-019-05928-5. View

3.
Huang S, Rutkowsky J, Snodgrass R, Ono-Moore K, Schneider D, Newman J . Saturated fatty acids activate TLR-mediated proinflammatory signaling pathways. J Lipid Res. 2012; 53(9):2002-13. PMC: 3413240. DOI: 10.1194/jlr.D029546. View

4.
Pan L, Yu L, Wang L, He J, Sun J, Wang X . The toll-like receptor 4 antagonist transforming growth factor-β-activated kinase(TAK)-242 attenuates taurocholate-induced oxidative stress through regulating mitochondrial function in mice pancreatic acinar cells. J Surg Res. 2016; 206(2):298-306. DOI: 10.1016/j.jss.2016.08.011. View

5.
Ji R, Chen Y, Chen W, Wang Y, Gong F, Huang S . Identification of Significant Genes and Pathways in Acute Pancreatitis via Bioinformatical Analysis. Dig Dis Sci. 2020; 66(9):3045-3053. DOI: 10.1007/s10620-020-06598-4. View