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Downregulation of CYP7B1 caused by lipotoxicity associates with the progression of non-alcoholic steatohepatitis

Watanabe, Y.; Kinoshita, K.; Dumrongkulchart, N.; Sasaki, T.; Shimizu, M.; Yamauchi, Y.; Sato, R.

2023-05-10 biochemistry
10.1101/2023.05.10.539979 bioRxiv
Show abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an incidence of >25% of the adult population. NAFLD ranges from benign simple steatosis to non-alcoholic steatohepatitis (NASH). However, its transition mechanisms underlying the pathogenesis remain to be clarified. The expression of Cyp7b1 gene is downregulated in the liver of leptin-deficient mice and methionine and choline-deficient diet-fed mice based on previous microarray data. Thus, in this study, we investigated the effect of CYP7B1 restoration on the progression of NASH in mice fed MCD diet and its association with oxidative and lipid stresses. Our results suggest that restoration of CYP7B1 expression attenuates hepatitis and fibrosis and that lipid and oxidative stresses observed in the early stage of NASH suppresses Cyp7b1 transcription in hepatocytes.

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