scholarly journals Nogo-B receptor deficiency increases liver X receptor alpha nuclear translocation and hepatic lipogenesis through an adenosine monophosphate-activated protein kinase alpha-dependent pathway

Hepatology ◽  
2016 ◽  
Vol 64 (5) ◽  
pp. 1559-1576 ◽  
Author(s):  
Wenquan Hu ◽  
Wenwen Zhang ◽  
Yuanli Chen ◽  
Ujala Rana ◽  
Ru-jeng Teng ◽  
...  
2020 ◽  
Author(s):  
Xuanjing Chen ◽  
Dezhi Zou ◽  
Xiaoling Chen ◽  
Huanlin Wu ◽  
Danping Xu

AbstractCholesterol efflux from macrophages is the first step of cholesterol reverse transport (RCT), whose increase inhibits cholesterol accumulation and foam cell formation to suppress atherogenesis. Liver X receptor alpha (LXRα) and adenosine monophosphate activated protein kinases (AMPK) both have the pivotal role in cholesterol homeostasis. However the association between these two molecules in cell model of atherosclerosis is poorly understood. Hesperetin has been reported to possess several protective effects for cardiovascular diseases, while little is known about the role of hesperetin and its underlying mechanism on macrophage foam cell formation. In this study, we sought to investigate the potential effects of hesperetin in cholesterol efflux by using human macrophage derived foam cells, focusing on liver X receptor alpha (LXRα) and adenosine monophosphate activated protein kinases (AMPK) implication. Hesperetin treatment concentration-dependently reduced foam cell formation, intracellular cholesterol level and cholesterol esterification rate, and enhanced cholesterol efflux in THP-1 macrophages. Hesperetin upregulated the protein levels of LXRα and its targets including ABCA1, ABCG1 as well as SR-BI, and phosphorylated-AMPK. Meanwhile, hesperetin-induced upregulation of LXRα expression was enhanced by AMPK agonist and inhibited by AMPK inhibitor. Furthermore, hesperetin increased mRNA level of LXRα and its target genes, all which were depressed by AMPKα1/α2 small interfering RNA (siRNA) transfection. In conclusion, we founded for the first time that hesperetin could active AMPK. And this activation upregulated LXRα and its targets including ABCA1, ABCG1 and SR-BI, which significantly inhibited foam cell formation and promoted cholesterol efflux in THP-1 macrophages. Our results highlight the therapeutic potential of hespretin for the possible reduction in foam cell formation. This new mechanism could contribute the anti-atherogenic effects of hesperetin.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Geng Chen ◽  
Shuodong Wu

This study was aimed at investigating the effect of baicalin on experimental cholesterol gallstones in mice. The mouse gallstone model was induced by feeding with a lithogenic diet, and cholesterol stones were found in the gallbladder. The lithogenic diet caused elevation of triglycerides, cholesterol, and low-density lipoprotein concentrations and descent of high-density lipoprotein concentration in serum. Hyperplasia and inflammatory infiltration were observed in the gallbladder wall of lithogenic diet-fed mice. We also found the increase of cholesterol content and the decrease of bile acid in bile. Real-time PCR and western blot results demonstrated that the expression levels of two enzymes (cholesterol 7α-hydroxylase (CYP7a1) and sterol 12α-hydroxylase (CYP8b1)) to catalyze the synthesis of bile acid from cholesterol were decreased and that two cholesterol transporters (ATP-binding cassette transporter G5/G8 (ABCG5/8)) were increased in the liver of lithogenic diet-fed mice. The lithogenic diet also led to enhanced activity of alanine aminotransferase and aspartate aminotransferase in serum; increased concentrations of tumor necrosis factor-α, interleukin- (IL-) 1β, IL-6, and malondialdehyde; and decreased superoxide dismutase activity in the liver, suggesting inflammatory and oxidative stress. In addition, liver X receptor alpha (LXRα) was increased in the liver. After gavage of baicalin, the lithogenic diet-induced gallstones, hyperlipidemia, gallbladder hyperplasia, inflammation, and oxidative stress in liver and cholesterol metabolism disorders were all alleviated to some degree. The expression of LXRα in the liver was inhibited by baicalin. In addition, the LXRα agonist T0901317 aggravated lithogenic diet-induced harmful symptoms in mice, including the increase of gallstone formation, hyperlipidemia, hepatic injury, inflammation, and oxidative stress. In conclusion, we demonstrated that baicalin played a protective role in a lithogenic diet-induced gallstone mouse model, which may be mediated by inhibition of LXRα activity. These findings may provide novel insights for prevention and therapy of gallstones in the clinic.


2011 ◽  
Vol 31 (12) ◽  
pp. 2990-2996 ◽  
Author(s):  
Stefan Stender ◽  
Ruth Frikke-Schmidt ◽  
Aristomenis Anestis ◽  
Dimitris Kardassis ◽  
Amar A. Sethi ◽  
...  

2012 ◽  
Vol 03 (02) ◽  
pp. 249-254 ◽  
Author(s):  
Abbas Mohammadi ◽  
Ebrahim Abbasi Oshaghi ◽  
Arash Noori Sorkhani ◽  
Farhad Oubari ◽  
Roghaye Hosseini Kia ◽  
...  

Lipids ◽  
2011 ◽  
Vol 47 (3) ◽  
pp. 249-257 ◽  
Author(s):  
Huihong Yu ◽  
Jinfeng Wu ◽  
Mei Yang ◽  
Jinjun Guo ◽  
Lili Zheng ◽  
...  

2018 ◽  
Vol 77 (OCE4) ◽  
Author(s):  
K. Nugraheni ◽  
S.A. Hutchinson ◽  
J.L. Thorne ◽  
C. Boesch

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