ArticleHepatology (Baltimore, Md.)2016
Nogo-B receptor deficiency increases liver X receptor alpha nuclear translocation and hepatic lipogenesis through an adenosine monophosphate-activated protein kinase alpha-dependent pathway.
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 34 citations in OpenAlex.
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- Depletion of essential isoprenoids and ER stress induction following acute liver-specific deletion of HMG-CoA reductase.Journal of lipid research · 2020Article
- Research advances on neurite outgrowth inhibitor B receptor.Journal of cellular and molecular medicine · 2020Review
- ER-residential Nogo-B accelerates NAFLD-associated HCC mediated by metabolic reprogramming of oxLDL lipophagy.Nature communications · 2019Article
- Epigenetically Down-Regulated Acetyltransferase PCAF Increases the Resistance of Colorectal Cancer to 5-Fluorouracil.Neoplasia (New York, N.Y.) · 2019Article
- Transplantation of HUVECs with genetically modified Nogo-B accelerates wound-healing in nude mice.American journal of translational research · 2019Article
- Nogo-B promotes tumor angiogenesis and provides a potential therapeutic target in hepatocellular carcinoma.Molecular oncology · 2018Article
- Functional interplay between liver X receptor and AMP-activated protein kinase α inhibits atherosclerosis in apolipoprotein E-deficient mice - a new anti-atherogenic strategy.British journal of pharmacology · 2018Article
- 25-Hydroxycholesterol activates the expression of cholesterol 25-hydroxylase in an LXR-dependent mechanism.Journal of lipid research · 2018Article
- Activation of hepatic Nogo-B receptor expression-A new anti-liver steatosis mechanism of statins.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018Article
- NGBR is required to ameliorate type 2 diabetes in mice by enhancing insulin sensitivity.The Journal of biological chemistryArticle
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Nogo-B receptor (NgBR) was identified as a specific receptor for binding Nogo-B and is essential for the stability of Niemann-Pick type C2 protein (NPC2) and NPC2-dependent cholesterol trafficking. Here, we report that NgBR expression levels decrease in the fatty liver and that NgBR plays previously unrecognized roles in regulating hepatic lipogenesis through NPC2-independent pathways. To further elucidate the pathophysiological role of NgBR in mammals, we generated NgBR liver-specific knockout mice and investigated the roles of NgBR in hepatic lipid homeostasis. The results showed that NgBR knockout in mouse liver did not decrease NPC2 levels or increase NPC2-dependent intracellular cholesterol levels. However, NgBR deficiency still resulted in remarkable cellular lipid accumulation that was associated with increased free fatty acids and triglycerides in hepatocytes in vitro and in mouse livers in vivo. Mechanistically, NgBR deficiency specifically promotes the nuclear translocation of the liver X receptor alpha (LXRα) and increases the expression of LXRα-targeted lipogenic genes. LXRα knockout attenuates the accumulation of free fatty acids and triglycerides caused by NgBR deficiency. In addition, we elucidated the mechanisms by which NgBR bridges the adenosine monophosphate-activated protein kinase alpha signaling pathway with LXRα nuclear translocation and LXRα-mediated lipogenesis.
conclusionNgBR is a specific negative regulator for LXRα-dependent hepatic lipogenesis. Loss of NgBR may be a potential trigger for inducing hepatic steatosis. (Hepatology 2016;64:1559-1576).
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