scholarly journals Front cover: Lycium barbarum Polysaccharide Supplementation Improves Alcoholic Liver Injury in Female Mice by Inhibiting Stearoyl-CoA Desaturase 1

2018 ◽  
Vol 62 (13) ◽  
pp. 1870072
Author(s):  
Fei Wang ◽  
George L. Tipoe ◽  
Changqing Yang ◽  
Amin A. Nanji ◽  
Xiangfeng Hao ◽  
...  
Keyword(s):  
Liver Injury ◽  
Alcoholic Liver Injury ◽  
Lycium Barbarum ◽  
Front Cover ◽  
Female Mice ◽  
Lycium Barbarum Polysaccharide ◽  
Stearoyl Coa Desaturase

scholarly journals Alcohol Consumption Accumulation of Monocyte Derived Macrophages in Female Mice Liver Is Interferon Alpha Receptor Dependent

2021 ◽  
Vol 12 ◽  
Author(s):  
Khaled Alharshawi ◽  
Holger Fey ◽  
Alyx Vogle ◽  
Tori Klenk ◽  
Miran Kim ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Liver Injury ◽  
Immune Cell ◽  
Tissue Injury ◽  
Alcohol Exposure ◽  
The United States ◽  
Alcoholic Liver Injury ◽  
Hematopoietic Stem ◽  
Female Mice ◽  
Inflammatory Conditions

Monocytes develop in the bone marrow from the hematopoietic stem cells and represent heterogeneous phagocyte cells in the circulation. In homeostatic and inflammatory conditions, after recruitment into tissues, monocytes differentiate into macrophages and dendritic cells. Alcohol use causes about 3.3 million worldwide deaths per year, which is about 5.9% of all deaths. In the United States and Europe, alcohol use disorders represent the fifth leading cause of death. Females are more susceptible to alcoholic liver injury in both humans and mice. Strikingly, we still do not know how much of this difference in tissue injury is due to the differential effect of alcohol and its toxic metabolites on a) parenchymal or resident cells and/or b) immune response to alcohol. Therefore, we used a model of chronic alcohol exposure in mice to investigate the dynamics of monocytes, an innate immune cell type showed to be critical in alcoholic liver injury, by using immunophenotypic characterization. Our data reveal a sex-dimorphism of alcohol response of hepatic monocytes in female mice that is interferon receptor alpha dependent. This dimorphism could shed light on potential cellular mechanism(s) to explain the susceptibility of females to alcoholic immunopathogenesis and suggests an additional targetable pathway for alcoholic liver injury in females.

scholarly journals Molecular mechanism for the influence of gender dimorphism on alcoholic liver injury in mice

2018 ◽  
Vol 38 (1) ◽  
pp. 65-81 ◽  
Author(s):  
S-Q Li ◽  
P Wang ◽  
D-M Wang ◽  
H-J Lu ◽  
R-F Li ◽  
...  
Keyword(s):  
Liver Injury ◽  
Molecular Mechanism ◽  
Sex Difference ◽  
B Cell Lymphoma ◽  
Alcoholic Liver Injury ◽  
Male Mice ◽  
Gender Dimorphism ◽  
Treated Male ◽  
Female Mice ◽  
Gene And Protein Expression

It is known that women develop alcoholic liver injury more rapidly and have a lower alcohol toxic threshold than men. However, the detailed molecular mechanisms remain unclear. The precise mechanism responsible for the sex difference needs to be determined. Female and male mice were given ethanol by intragastric infusion every day for 4 weeks. The pathological changes were detected by hematoxylin–eosin, Sirius red, oil red O, periodic acid–Schiff, and Hochest33258 staining in the liver of female and male mice. The related gene and protein expression of hepatocytes stress, proliferation and apoptosis, glycogen synthesis, lipid metabolism, and hepatic fibrosis were also systematically analyzed in the female and male mice. Livers from ethanol-treated female mice had more serious hepatocyte necrosis, liver fibrosis ( P < 0.01), substantial micro/macrovesicular steatosis ( p < 0.01), glycogen consumption ( p < 0.05), and hepatocytes apoptosis ( p < 0.05) than ethanol-treated male mice. The expression of heat shock protein 27 (HSP27), HSP70, proliferating cell nuclear antigen, B-cell lymphoma/leukemia-2 (Bcl-2), and phosphorylated signal transducer and activators of transcription 3 (p-STAT3) was higher in ethanol-treated male mice than ethanol-treated female mice ( P < 0.05 or P < 0.01). But, the expression of Bax (Bcl-2-associated X protein), Caspase 3, CYP2E1 (cytochrome P4502E1), and transforming growth factor βl had the contrary results. Our study suggested that ethanol treatment induced more expression of HSP27 and HSP70, faster hepatocyte proliferation, higher level of glycogen, and interleukin-6 signaling pathway activation, but less hepatocyte apoptosis and CYP2E1 expression in male mice than female mice, which could be helpful to understand the molecular mechanism for the influence of sex difference on alcoholic liver injury.

scholarly journals Characterizing the Role of HMG-CoA Reductase in Aryl Hydrocarbon Receptor-Mediated Liver Injury in C57BL/6 Mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Peter Dornbos ◽  
Amanda Jurgelewicz ◽  
Kelly A. Fader ◽  
Kurt Williams ◽  
Timothy R. Zacharewski ◽  
...  
Keyword(s):  
Liver Injury ◽  
Aryl Hydrocarbon Receptor ◽  
Cholesterol Biosynthesis ◽  
Competitive Inhibitor ◽  
Cholesterol Homeostasis ◽  
Hepatic Glycogen ◽  
Alcoholic Fatty Liver ◽  
Female Mice ◽  
Aryl Hydrocarbon ◽  
The Impact

Abstract The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. The prototypical ligand of the AHR is an environmental contaminant called 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD exposure is associated with many adverse health outcomes in humans including non-alcoholic fatty liver disease (NAFLD). Previous studies suggest that AHR ligands alter cholesterol homeostasis in mice through repression of genes involved in cholesterol biosynthesis, such as Hmgcr, which encodes the rate-limiting enzyme of cholesterol biosynthesis called 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR). In this study, we sought to characterize the impact of HMGCR repression in TCDD-induced liver injury. C57BL/6 mice were exposed to TCDD in the presence or absence of simvastatin, a competitive inhibitor of HMGCR. Simvastatin exposure decreased TCDD-induced hepatic lipid accumulation in both sexes, but was most prominent in females. Simvastatin and TCDD (S + T) co-treatment increased hepatic AHR-battery gene expression and liver injury in male, but not female, mice. In addition, the S + T co-treatment led to an increase in hepatic glycogen content that coincides with heavier liver in female mice. Results from this study suggest that statins, which are amongst the most prescribed pharmaceuticals, may protect from AHR-mediated steatosis, but alter glycogen metabolism and increase the risk of TCDD-elicited liver damage in a sex-specific manner.

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