Important roles of UGT2B28, FABP5, and CYP2C9 in the development of rat liver fibrosis induced by abnormal fatty acid metabolism

Abstract

Abstract: Objective Purpose Abnormal fatty acid metabolism has been found to be one of the mechanisms of dimethylnitrosamine (DMN)-induced hepatic fibrosis. In this study, we further elucidated the key regulatory genes of fatty acid metabolism in DMN-induced rat model of hepatic fibrosis. Methods The classical rat model of DMN-induced liver fibrosis was replicated. Serum and liver tissues were collected at 2 and 4 weeks of modeling. The serum samples were analyzed for liver function and lipid metabolism. Whole gene microarray was performed with the liver tissues and the microarray data were deeply mined with bioinformatic analysis software. Results Serum ALT and AST levels were (25.28 ± 3.03)U/L and (69.17 ± 5.20)U/L, and (45.83 ± 5.03)U/L and (108.10 ± 17.31)U/L in the model group at 2 weeks and 4 weeks of modeling, respectively, which was significantly higher than those of (25.28 ± 3.03)U/L and (61.44 ± 11.82)U/L in the control group (P<0.05); Similarly, serum TG and FFA levels were (1.11 ± 0.30) and (0.26 ± 0.04), and (0.77 ± 0.10) and (0.49 ± 0.18) mmol/L in the model group at 2 weeks and 4 weeks of modeling, respectively, which was significantly higher than (0.77 ± 0.22) and (0.51 ± 0.18) mmol/L in the control group (P<0.01 for TG, and P<0.05 for FFA). There were 55 shared differential genes (Log Ratio >2) were identified, which were enriched in 9 signaling pathways associated with cell proliferation, fatty acid metabolism, apoptosis, cell death and other biological functions. The shared differential gene UGT2B28 was significantly up-regulated (>5-fold) in 2 weeks and 4 weeks liver samples of the model group, while FABP5 in the liver samples of the model group at 2 weeks and CYP2C9 in the liver samples of the model group at 4 weeks were significantly up-regulated (>5-fold). UGT2B28, FABP5 and CYP2C9 were involved in all processes of lipid metabolism. Conclusion The shared differential genes UGT2B28, FABP5 and CYP2C9 play key roles in the mechanism of liver fibrogenesis associated with abnormal fatty acid metabolism.

Key words: Hepatic fibrosis, Fatty acid metabolism, Bioinformatic analysis, Dimethylnitrosamine

SONG Jing-ru, WU Chao, CAO Hong-yan, XIE Dong, WANG Zheng, LIU Lu, WANG Dan, SUN Ming-yu, BIAN Yan-qin. Important roles of UGT2B28, FABP5, and CYP2C9 in the development of rat liver fibrosis induced by abnormal fatty acid metabolism[J]. Chinese Hepatolgy, 2022, 27(9): 999-1003.

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