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Liver X Receptors Regulate Cholesterol Metabolism and Immunity in Hepatic Nonparenchymal Cells

Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, 30-1 Oyaguchi-kamicho, Itabashi-ku, Tokyo 173-8610, Japan
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Int. J. Mol. Sci. 2019, 20(20), 5045; https://doi.org/10.3390/ijms20205045
Received: 15 September 2019 / Revised: 6 October 2019 / Accepted: 9 October 2019 / Published: 11 October 2019
(This article belongs to the Special Issue Liver X Receptors)
Excess dietary cholesterol intake and the dysregulation of cholesterol metabolism are associated with the pathogenesis and progression of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and fibrosis. Hepatic accumulation of free cholesterol induces activation of nonparenchymal cells, including Kupffer cells, macrophages, and hepatic stellate cells, which leads to persistent inflammation and fibrosis. The nuclear receptors liver X receptor α (LXRα) and LXRβ act as negative regulators of cholesterol metabolism through the induction of hepatocyte cholesterol catabolism, excretion, and the reverse cholesterol transport pathway. Additionally, LXRs exert an anti-inflammatory effect in immune cell types, such as macrophages. LXR activation suppresses acute hepatic inflammation that is mediated by Kupffer cells/macrophages. Acute liver injury, diet-induced steatohepatitis, and fibrosis are exacerbated by significant hepatic cholesterol accumulation and inflammation in LXR-deficient mice. Therefore, LXRs regulate hepatic lipid metabolism and immunity and they are potential therapeutic targets in the treatment of hepatic inflammation that is associated with cholesterol accumulation. View Full-Text
Keywords: cholesterol; liver X receptor; hepatic nonparenchymal cell; Kupffer cell; macrophage; NAFLD; NASH; hepatic fibrosis cholesterol; liver X receptor; hepatic nonparenchymal cell; Kupffer cell; macrophage; NAFLD; NASH; hepatic fibrosis
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Endo-Umeda, K.; Makishima, M. Liver X Receptors Regulate Cholesterol Metabolism and Immunity in Hepatic Nonparenchymal Cells. Int. J. Mol. Sci. 2019, 20, 5045.

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