The present study aimed to compare the effects of polyunsaturated fat and saturated fat on alcoholic liver disease (ALD) and explore the underlying mechanisms. C57BL/6J male mice were randomly fed corn oil or palm oil diet (rich in polyunsaturated and saturated fatty acids, respectively) with or without ethanol for 4 weeks (n = 10 per group). Early stage of ALD was developed with Lieber-DeCarli liquid diet. Compared with palm oil, corn oil aggravated alcohol-induced liver injury and hepatic steatosis, indicated by histological analysis and significant elevations of plasma alanine aminotransferase level and hepatic triacylglycerol (TG) level. Apoptosis-associated proteins in ASK1-JNK pathway and proteins involved in lipid synthesis in AMPK signaling pathway, were significantly enhanced in liver of mice from corn oil + ethanol group than that from palm oil + ethanol group. In addition, plasma and liver levels of 4-hydroxynonenal (4-HNE) were significantly increased in response to corn oil + ethanol feeding. Interestingly, linoleic acid, the primary fatty acid in corn oil, up-regulated the production of 4-HNE <i>in vitro</i> in AML-12 hepatocyte, compared with palmitic acid, the predominant fatty acid in palm oil. And 4-HNE significantly attenuated cell viability, elevated the expression of cleaved-Caspase 3 protein and TG level, and regulated key molecules in ASK1-JNK and AMPK pathways in a dose-depend manner. In conclusion, diet rich in polyunsaturated fat showed negative effect on alcohol-induced liver injury and hepatic steatosis, and this effect might be related to the up-regulation of 4-HNE and subsequent changes of key proteins in ASK1-JNK and AMPK signaling pathways.

Upregulation of 4-hydroxynonenal contributes to the negative effect of polyunsaturated fatty acid on alcohol-induced liver injury and hepatic steatosis

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ACS Fall 2022

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