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J Clin Biochem Nutr. 2014 Mar;54(2):90-4. doi: 10.3164/jcbn.13-92. Epub 2014 Feb 14.

Role of Nrf2 in the alteration of cholesterol and bile acid metabolism-related gene expression by dietary cholesterol in high fat-fed mice.

Author information

1
Department of Clinical Laboratory Medicine, Kinki University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan.
2
Department of Clinical Laboratory Medicine, Kinki University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan ; Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
3
Faculty of Human Sciences, Tezukayama Gakuin University, Sakai, Osaka 590-0113, Japan.
4
Division of Basic Medical Science, Kinki University Faculty of Medicine, Osakasayama, Osaka 589-8511, Japan.

Abstract

Nuclear factor-E2-related factor 2 (Nrf2) is a regulator of lipid metabolism as well as various cytoprotective enzymes and may be involved in the pathogenesis of non-alcoholic fatty liver disease. Although, bile acids affect lipid metabolism, the role of Nrf2 in bile acid metabolism remains unclear. In this study, it was tested how Nrf2 modulates lipid and bile acid homeostasis in liver in response to changes of cholesterol absorption under high-fat diet using Nrf2-null mice. Eight-week-old male wild-type and Nrf2-null mice (n = 6/group) were divided into three groups fed the following diets: 1) control diet containing 4% soybean oil and 16% lard, 2) control diet plus ezetimibe, 3) control diet plus cholesterol. Blood and livers were removed after 4 weeks feeding. High cholesterol diet increased hepatic expression of liver X receptor α target genes related to fatty acid metabolism (FAS, ACC1, SREBP-1c, SCD-1c and CD36), cholesterol transport (Abcg5/abcg8) and bile acid synthesis (Cyp7a1) in wild type mice. However, these genes were not induced in Nrf2-null mice. These findings suggest that Nrf2 has a relation to liver X receptor α and controls the regulation of gene expressions related to lipid and bile acid metabolism.

KEYWORDS:

bile acid metabolism; cholesterol metabolism; liver X receptor α; non-alcoholic fatty liver disease; nuclear factor-E2-related factor 2

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