scholarly journals NLRP6 Inflammasome Modulates Disease Progression in a Chronic-Plus-Binge Mouse Model of Alcoholic Liver Disease

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 182
Author(s):  
Rebecca Elena Mainz ◽  
Stefanie Albers ◽  
Madhuri Haque ◽  
Roland Sonntag ◽  
Nicole Simone Treichel ◽  
...  
Keyword(s):  
Liver Disease ◽  
Mouse Model ◽  
Alcoholic Liver Disease ◽  
Immune Cell ◽  
Liver Steatosis ◽  
Neutrophil Infiltration ◽  
Ethanol Administration ◽  
Intestinal Homeostasis ◽  
Binge Ethanol

A considerable percentage of the population is affected by alcoholic liver disease (ALD). It is characterized by inflammatory signals from the liver and other organs, such as the intestine. The NLR family pyrin domain containing 6 (NLRP6) inflammasome complex is one of the most important inflammatory mediators. The aim of this study was to evaluate a novel mouse model for ALD characterized by 8-week chronic-plus-binge ethanol administration and to investigate the role of NLRP6 inflammasome for intestinal homeostasis and ALD progression using Nlrp6-/- mice. We showed that chronic-plus-binge ethanol administration triggers hepatic steatosis, injury, and neutrophil infiltration. Furthermore, we discovered significant changes of intestinal microbial communities, including increased relative abundances of bacteria within the phyla Bacteroidota and Campilobacterota, as well as reduced Firmicutes. In this ALD model, inhibiting NLRP6 signaling had no effect on liver steatosis or damage, but had a minor impact on intestinal homeostasis via affecting intestinal epithelium function and gut microbiota. Surprisingly, Nlrp6 loss resulted in significantly decreased hepatic immune cell infiltration. As a result, our novel mouse model encompasses several aspects of human ALD, such as intestinal dysbiosis. Interfering with NLRP6 inflammasome activity reduced hepatic immune cell recruitment, indicating a disease-aggravating role of NLRP6 during ALD.

scholarly journals Rodent Models of Alcoholic Liver Disease: Role of Binge Ethanol Administration

Biomolecules ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 3 ◽  
Author(s):  
Shubha Ghosh Dastidar ◽  
Jeffrey Warner ◽  
Dennis Warner ◽  
Craig McClain ◽  
Irina Kirpich
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Ethanol Administration ◽  
Rodent Models ◽  
Binge Ethanol

scholarly journals C57BL/6 and A/J Mice Have Different Inflammatory Response and Liver Lipid Profile in Experimental Alcoholic Liver Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Lorena Bavia ◽  
Íris Arantes de Castro ◽  
Lourdes Isaac
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Genetic Background ◽  
Inflammatory Responses ◽  
Liver Lipid ◽  
Liver Steatosis ◽  
Public Health Issue ◽  
Mouse Strains ◽  
Mice Liver

Alcoholic liver disease (ALD) is an important worldwide public health issue characterized by liver steatosis, inflammation, necrosis, and apoptosis of hepatocytes with eventual development of fibrosis and cirrhosis. Comparison of murine models with different inflammatory responses for ALD is important for an evaluation of the importance of genetic background in the interpretation of ethanol-induced phenotypes. Here, we investigated the role of inflammation and genetic background for the establishment of ALD using two different mouse strains: C57BL/6 (B6) and A/J. B6 and A/J mice were treated with a high fat diet containing ethanol (HFDE) and compared to the controls for 10 weeks. Hepatomegaly and steatohepatitis were similar in B6 and A/J mice, but only A/J mice were resistant to weight gain. On the other hand, HFDE-fed B6 accumulated more triglycerides (TG) and cholesterol and presented more intense cellular infiltrate in the liver when compared to HFDM-fed mice. Liver inflammatory environment was distinct in these two mouse strains. While HFDE-fed B6 produced more liver IL-12, A/J mice increased the TNF-αproduction. We concluded that mouse genetic background could dictate the intensity of the HFDE-induced liver injury.

scholarly journals The lymphatic system in alcohol-associated liver disease

2020 ◽  
Vol 26 (4) ◽  
pp. 633-638
Author(s):  
Reiichiro Kondo ◽  
Yasuko Iwakiri
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Fluid Balance ◽  
Interstitial Fluid ◽  
Lymphatic System ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Review Article ◽  
Related Disease

The lymphatic system plays vital roles in interstitial fluid balance and immune cell surveillance. The effect of alcohol on the lymphatic system is poorly understood. This review article explores the role of the lymphatic system in the pathogenesis of alcohol-related disease including alcoholic liver disease (ALD) and the therapeutic potential of targeting hepatic lymphatics for the treatment of ALD.

Regulatory effect of volatile compounds in fermented alcoholic beverages on gut microbiota and serum metabolism in mouse model

2021 ◽  
Author(s):  
Mei Ji ◽  
Cheng Fang ◽  
Wei Jia ◽  
Hai Du ◽  
Yan Xu
Keyword(s):  
Risk Factor ◽  
Liver Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Volatile Compounds ◽  
Alcoholic Liver Disease ◽  
Alcoholic Beverages ◽  
Regulatory Effect ◽  
Main Risk Factor

Ethanol (EtOH) is the main risk factor for alcoholic liver disease. However, fermented alcoholic beverages contain not only ethanol but also various volatile compounds. Currently, effects of volatile compounds in...

scholarly journals Role of autophagy in the pathogenesis of liver diseases

2011 ◽  
Vol 152 (49) ◽  
pp. 1955-1961 ◽  
Author(s):  
Klára Werling
Keyword(s):  
Endoplasmic Reticulum ◽  
Liver Disease ◽  
Liver Diseases ◽  
Liver Tumors ◽  
Liver Steatosis ◽  
Prognostic Significance ◽  
Adenosine Monophosphate ◽  
Mutant Proteins ◽  
Alpha 1 Antitrypsin Deficiency

Autophagy is a self-digestion process that plays an important role in the development, differentiation and homeostasis of cells, helping their survival during starvation and hypoxia. Accumulated mutant proteins in the endoplasmic reticulum can be degraded by autophagy in alpha-1 antitrypsin deficiency. Hepatitis C and B virus may exploit the autophagy pathway to escape the innate immune response and to promote their own replication. Autophagy is decreased in response to chronic alcohol consumption, likely due to a decrease in 5’-adenosine monophosphate-activated protein kinase, increase in mTOR activity and due to an alteration in vesicle transport in hepatocytes. In obesity and alcoholic liver disease the decreased function of autophagy causes formation of Mallory-Denk bodies and cell death. The deficient autophagy can contribute to liver steatosis, to endoplasmic reticulum stress, and to progression of liver disease. Autophagy defect in hepatocellular carcinoma suggests that it can serve a tumor-suppressor function. The autophagy protein Beclin-1 levels have prognostic significance in liver tumors. Understanding of the molecular mechanism and the role of autophagy may lead to more effective therapeutic strategies in liver diseases in the future. Orv. Hetil., 2011, 152, 1955–1961.

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