Mechanism study of liver steatosis induced by amiodarone via PPARα signaling pathway

Abstract

Abstract: Objective To investigate the mechanism of hepatic steatosis induced by amiodarone. Methods Male C57BL/6J mice aged 8 weeks were divided into 3 groups of 5.control group with normal diet (WT group, n=5); Amiodarone at 150mg.kg-1.d-1 was administered intragastatically for 10 days as the model group (AM group, n=5). In the intervention group (AM+PPARα agonist WY14643 (2.5mg/kg), n=5) amiodarone was used simultaneously by gavage with WY14643 (2.5mg/kg) for 10 consecutive days;After 10 day, serum alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol and high density lipoprotein in each group were detected.The pathological changes of liver were observed by HE staining and oil red staining. The expression of PPARαand its regulated lipid metabolism genes were detected by RT-PCR. t test was used for intra-group comparison, one-way analysis of variance was used for inter-group comparison, and Mann-Whitney U test for non-parametric test was used for semi-quantitative data. Results Pathological observation showed that compared with the model group, the results of liver oil red and HE staining in the intervention group showed that the liver fat change was significantly reduced ;RT-PCR results showed that mRNA expression of PPARαand downstream related genes CPTI, Cyp4a14, Acot1decreased in amiodarone group. After treatment, the expressions of PPARα and some related genes were increased compared with those of model group ((P=0.0003, 0.0157, 0.0057, 0.0203). Conclusion Amiodarone may induce liver steatosis by regulating PPARα and its downstream related genes.

Key words: Amiodarone, Fatty liver, Mitochondria, PPARα

SUN Shuang-shuang,TAO Shuai,TANG Xi-xi,FU Qing-chun. Mechanism study of liver steatosis induced by amiodarone via PPARα signaling pathway[J]. Chinese Hepatolgy, 2023, 28(7): 818-822.

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