Fc gamma RIIb expression levels in human liver sinusoidal endothelial cells during progression of non-alcoholic fatty liver disease

NAFLD is the most prevalent liver disorder worldwide, involving pathogenic mechanisms of liver sinusoidal endothelial cells (LSECs), hepatocytes and other liver cells.

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Water Extract of Curcuma longa L. Ameliorates Non-Alcoholic Fatty Liver Disease

Nutrients ◽

10.3390/nu11102536 ◽

2019 ◽

Vol 11 (10) ◽

pp. 2536 ◽

Cited By ~ 6

Author(s):

Jeongeun Mun ◽

Shintae Kim ◽

Ho-Geun Yoon ◽

Yanghee You ◽

Ok-Kyung Kim ◽

...

Keyword(s):

Fatty Acid ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Curcuma Longa ◽

Water Extract ◽

Hot Water ◽

Alcoholic Fatty Liver ◽

Expression Levels ◽

Alcoholic Fatty Liver Disease

Our aim was to investigate whether hot water extract (CLW) of Curcuma longa L. could prevent non-alcoholic fatty liver disease (NAFLD). HepG2 cells were treated with free fatty acid (FFA) mixture (oleic acid: palmitic acid, 2:1) for 24 h to stimulate in vitro fatty liver. In addition, C57BL/6 mice were fed 60 kcal% high-fat (HF) diet for eight weeks to induce fatty liver in vivo. Intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) productions were increased by FFA and HF-diet, but supplementation with CLW significantly decreased these levels. CLW treatment ameliorated antioxidant activities that were suppressed by exposure to the FFA and HF-diet. Cluster of differentiation 36 (CD36) and fatty acid transport proteins (FATP2 and FATP5) were increased in HF-diet groups, while CLW suppressed their expression levels. Moreover, sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-coenzyme A carboxylase (ACC), and fatty acid synthase (FAS) expression levels were down-regulated in the CLW groups compared to HF-diet groups. On the other hand, 5′ adenosine monophosphate-activated protein kinase (AMPK), Peroxisome proliferator-activated receptor alpha (PPAR-α), and carnitine palmitoyltransferase 1 (CPT-1) expressions were up-regulated in the CLW groups. HF-diet fed mice showed high hepatic triglycerides (TG) content compared to the normal diet mice. However, the administration of CLW restored the hepatic TG level, indicating an inhibitory effect against lipid accumulation by CLW. These results suggest that CLW could be a potentially useful agent for the prevention of NAFLD through modulating fatty acid uptake.

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Analysis of non-alcoholic fatty liver disease (NAFLD) transcriptomic signatures in human liver

Signaling Pathways Project Datasets ◽

10.1621/k8wfimy9pe ◽

2016 ◽

Author(s):

H Jochen

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Human Liver ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

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High-content hydrogen water-induced downregulation of miR-136 alleviates non-alcoholic fatty liver disease by regulating Nrf2 via targeting MEG3

Biological Chemistry ◽

10.1515/hsz-2017-0303 ◽

2018 ◽

Vol 399 (4) ◽

pp. 397-406 ◽

Cited By ~ 7

Author(s):

Xiang Wang ◽

Jiao Wang

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Cellular Model ◽

Mice Model ◽

Alcoholic Fatty Liver ◽

Expression Levels ◽

Hydrogen Water ◽

Qrt Pcr ◽

Alcoholic Fatty Liver Disease

AbstractThis study was aimed to investigate the potential regulatory mechanism of high-content hydrogen water (HHW) in non-alcoholic fatty liver disease (NAFLD). A high-fat diet (HFD)-induced NAFLD mice model and cellular model were prepared. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TCH) and triglycerides (TG) were measured. The expression levels of representative five microRNA (miRNAs) (miR-103, miR-488, miR-136, miR-505 and miR-148a) in liver tissues were determined by quantitative real-time PCR (qRT-PCR). The target of miR-136 was validated by RNA immunoprecipitation (RIP) and pull-down assay. MiR-136, MEG3 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression levels following cell treatment were detected in hepatocytes using qRT-PCR and Western blotting. Moreover, cell viability and TG content were conducted. MiR-136 was downregulated, MEG3 as well as Nrf2 was upregulated and serum lipid level was reduced in NAFLD mice model after HHW treatment, which exerted the same effect in cellular model. RIP and RNA pull-down assay confirmed that MEG2 was a downstream target of miR-136. What’s more, HHW ameliorated lipid accumulation by regulating miR-136/MEG3/Nrf2 axisin vitroandin vivo. Hence, HHW alleviated NAFLD by downregulation of miR-136 through mediating Nrf2 via targeting MEG3.

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Targeting Liver Sinusoidal Endothelial Cells: An Attractive Therapeutic Strategy to Control Inflammation in Nonalcoholic Fatty Liver Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.655557 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xue-Kai Wang ◽

Zong-Gen Peng

Keyword(s):

Endothelial Cells ◽

Liver Disease ◽

Drug Development ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Liver Inflammation ◽

Liver Sinusoidal Endothelial Cells ◽

Sinusoidal Endothelial Cells ◽

Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD), especially its advanced stage nonalcoholic steatohepatitis (NASH), has become a threatened public health problem worldwide. However, no specific drug has been approved for clinical use to treat patients with NASH, though there are many promising candidates against NAFLD in the drug development pipeline. Recently, accumulated evidence showed that liver sinusoidal endothelial cells (LSECs) play an essential role in the occurrence and development of liver inflammation in patients with NAFLD. LSECs, as highly specialized endothelial cells with unique structure and anatomical location, contribute to the maintenance of liver homeostasis and could be a promising therapeutic target to control liver inflammation of NAFLD. In this review, we outline the pathophysiological roles of LSECs related to inflammation of NAFLD, highlight the pro-inflammatory and anti-inflammatory effects of LSECs, and discuss the potential drug development strategies against NAFLD based on targeting to LSECs.

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Combination of CCl4 with alcoholic and metabolic injuries mimics human liver fibrosis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00361.2018 ◽

2019 ◽

Vol 317 (2) ◽

pp. G182-G194 ◽

Cited By ~ 7

Author(s):

Maximilian Joseph Brol ◽

Felicitas Rösch ◽

Robert Schierwagen ◽

Fernando Magdaleno ◽

Frank Erhard Uschner ◽

...

Keyword(s):

Liver Disease ◽

Carbon Tetrachloride ◽

Liver Fibrosis ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Human Liver ◽

Alcoholic Fatty Liver ◽

Significant Fibrosis ◽

Alcoholic Fatty Liver Disease ◽

Significant Liver Fibrosis

Metabolic and alcoholic liver injuries result in nonalcoholic (NAFLD) or alcoholic (ALD) fatty liver disease, respectively. In particular, presence of fibrosis in NAFLD and ALD requires treatment, but development of drugs is hampered by the lack of suitable models with significant fibrosis. The carbon tetrachloride (CCl4) liver fibrosis model does not reflect human NAFLD or ALD, but CCl4 may serve as a fibrosis accelerator in addition to another injury. Ethanol in drinking water (16%) or Western diet (WD) were administered for 7 wk in mice either alone or in combination with CCl4 intoxications. Extent of fibrosis, steatosis, and inflammation was assessed by histology, transcription, and biochemistry. Furthermore, transcription of fibrosis, proliferation, and inflammation-related genes was studied on human liver samples with fibrosis resulting from hepatitis C virus infection ( n = 7), NAFLD ( n = 8), or ALD ( n = 7). WD or ethanol alone induced only mild steatosis and inflammation. Combination of CCl4 and WD induced the most severe steatosis together with significant liver fibrosis and moderate inflammation. Combination of CCl4 and ethanol induced the strongest inflammation, with significant liver fibrosis and moderate steatosis. The relationship pattern between fibrosis, proliferation, and inflammation of human ALD was mostly similar in mice treated with CCl4 and ethanol. The combination of CCl4 intoxication with WD validates previous data suggesting it as an appropriate model for human nonalcoholic steatohepatitis. Especially, CCl4 plus ethanol for 7 wk induces ALD in mice, providing a model suitable for further basic research and drug testing. NEW & NOTEWORTHY Alcoholic fatty liver disease with significant fibrosis is generated within 7 wk using carbon tetrachloride as a fibrosis accelerator and administering gradually ethanol (up to 16%) in mice. The similarity in the pattern of steatosis, inflammation, and fibrosis involved in alcoholic fatty liver disease to those of the human condition renders this mouse model suitable as a preclinical model for drug development.

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