Activation of hepatic Nogo-B receptor expression—A new anti-liver steatosis mechanism of statins

Abstract

Deficiency of hepatic Nogo-B receptor (NgBR) expression activates liver X receptor α (LXRα) in an adenosine monophosphate-activated protein kinase α (AMPKα)-dependent manner, thereby inducing severe hepatic lipid accumulation and hypertriglyceridemia. Statins have been demonstrated non-cholesterol lowering effects including anti-nonalcoholic fatty liver disease (NAFLD). Herein, we investigated if the anti-NAFLD function of statins depends on activation of NgBR expression. In vivo, atorvastatin protected apoE deficient or NgBR floxed, but not hepatic NgBR deficient mice, against Western diet (WD)-increased triglyceride levels in liver and serum. In vitro, statins reduced lipid accumulation in nonsilencing small hairpin RNA-transfected Conflict of interestNone declared. Transparency documentThe http://dx.doi.org/10.1016/j.bbalip.2017.12.002 associated with this article can be found, in online version. HHS Public Access

Simvastatin Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in Nonalcoholic Steatohepatitis Experimental Model

“…Statins (3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitor) are used worldwide for the treatment of lipid disorders; in particular, they reduce the high levels of low-density lipoprotein cholesterol (LDL-C), decreasing thus cardiovascular events and mortality [7]. However, there are accumulating data in the literature suggesting that statins, such as simvastatin (SIM), may also exert anti-inflammatory effects, such as inhibition of cytokine formation, adhesion molecule expression, and reduction of nitric oxide production [8–11], all of which could be of value in protecting against pathological inflammation and tissue damage.…”

Nogo‑B receptor in relevant carcinoma: Current achievements, challenges and aims (Review)

“…Ultimately, the activation of ACC-1 and AMPKα represses the expression of FASN, SREBP-1c and stearoyl coenzyme A desaturase-1 and enhances the levels of FFA and TG. Furthermore, the activation of AMPKα may rescue the translocation of LXRα mediated by a NgBR deficiency to ensure the maintenance of lipid metabolism (11,69). These results suggest that NgBR is able to mediate AMPKα in order to impact lipid homeostasis and LXRα.…”

“…1. Numerous pathophysiologic studies have confirmed that NgBR serves an important role in carcinogenesis and that its activation promotes cell proliferation and migration and inhibits apoptosis via multiple physiopathological mechanisms, including the AMPKα (11,69), LXRα (11,69), Akt (20,43) and ERK (28,43) signalling pathways.…”

NGBR is required to ameliorate type 2 diabetes in mice by enhancing insulin sensitivity

“…HepG2 cells, a human hepatic cell line (ATCC HB-8065), was purchased from ATCC and cultured in complete DMEM medium. The AMPKα1 genome knockout HepG2 cell line was generated using the clustered regulatory interspaced short palindromic repeat (CRISPR)-associated 9 (Cas9) technology as described (56,57). Mouse primary hepatocytes were isolated from C57BL/6 mouse liver as previously described (56).…”