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

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.

The “dose” of exercise and its effects beyond weight loss

“…12 Also relevant to NAFLD/NASH, Nrf2 appears to have a role in glucose and bile acid metabolism, though these roles are less well defined. 13,14 Thus, exercise-induced changes in Nrf2 could explain the beneficial effects of exercise independent of weight loss shown here and by others ( Fig. 1).…”

“…Up‐regulation of Nrf2 could conceivably decrease hepatic fibrosis as well by down‐regulation of transforming growth factor beta (TGF‐β) . Also relevant to NAFLD/NASH, Nrf2 appears to have a role in glucose and bile acid metabolism, though these roles are less well defined . Thus, exercise‐induced changes in Nrf2 could explain the beneficial effects of exercise independent of weight loss shown here and by others (Fig.…”

Pre-germinated brown rice extract ameliorates high-fat diet-induced metabolic syndrome

“…All of these changes were observed in this study (Figure 4). With regard to the proteins involved in lipid metabolism proteins, LDLR is a carrier that removes cholesterol and regulates its amount (Kamisako et al, 2014). PCSK9 binds to LDLR, in which LDL particles cannot be transferred into the cells (Kamisako et al, 2014;Nozue, 2017).…”

“…With regard to the proteins involved in lipid metabolism proteins, LDLR is a carrier that removes cholesterol and regulates its amount (Kamisako et al, 2014). PCSK9 binds to LDLR, in which LDL particles cannot be transferred into the cells (Kamisako et al, 2014;Nozue, 2017). The enzyme CYP7α1 is important for the synthesis of bile acid and the regulation of cholesterol levels (Chiu, Chang, Liu, & Chiang, 2017;Mohammadi et al, 2017).…”

Sexual dimorphic expression and release of transcription factors in bovine embryos exposed to oxidative stress

“…The molecular defense mechanisms involve the nuclear factor 2 (erythroid-derived 2) (NRF2 or NFE2L2) signaling pathway and the antioxidants machinery, which is reported to be vital for the survival of embryos under OS conditions (Amin et al, 2014;Leite et al, 2017). The NFE2L2 as TF can bind and regulate other TFs such as sterol regulatory element-binding transcription factors (SREBFs; Amin et al, 2014;Kamisako et al, 2014), notch receptor 1 (NOTCH1; Zhao et al, 2016), and pluripotency-related genes (Jang, Wang, Kim, Lalli, & Kosik, 2014).…”