Nuclear factor (erythroid-derived 2)-like 2 activation-induced hepatic very-low-density lipoprotein receptor overexpression in response to oxidative stress contributes to alcoholic liver disease in mice

• DOI: 10.1002/hep.26912
• Publication Date: 2013-10-29T11:18:47Z
• Authors: Zhigang Wang; Xiaobing Dou; Songtao Li; Ximei Zhang; Xinguo Sun; Zhanxiang Zhou; Zhenyuan Song
• Keywords: Steatosis

Chronic alcohol consumption leads to hypertriglyceridemia, which is positively associated with alcoholic liver disease (ALD). However, whether and how it contributes the development of fatty injury are largely unknown. In this study we demonstrate that chronic exposure differently regulates expression very-low-density lipoprotein receptor (VLDLR) in adipose tissue liver. Whereas VLDLR significantly down-regulated, its hepatic dramatically increased after feeding. While HepG2 cells stably overexpressing manifests intracellular triglyceride accumulation, VLDLR-deficient mice protective against exposure. Mechanistic investigations using both vitro vivo systems reveal oxidative stress-induced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation plays a critical role alcohol-induced up-regulation hepatocytes, but not adipocytes. Oxidative stress enhances gene protein abundance primary concomitant Nrf2 activation. Conversely, silencing abrogates liver, tissue. mice, induces Supplementation N-acetylcysteine alleviates induced by exposure, suppressed attenuated increase Furthermore, comparison wild-type counterparts, Nrf2-deficient response exposure.Chronic alters mechanistically involved overexpression hepatocytes consumption. Hepatic an important pathogenesis ALD.