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Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Transcriptome analysis of garlic-induced hepatoprotection against alcoholic fatty liver
Rajasekaran Raghu1, Chun-Ting Liu, Mong-Hsun Tsai
1Institute of Food Science and Technology, National Taiwan University, Taipei 106, Taiwan.
Abstract:
Fatty liver induced by alcohol abuse is a major worldwide health hazard leading to morbidity and mortality. Previous studies indicate antifatty liver properties of garlic. This study investigated the molecular mechanisms of garlic oil (GO) or diallyl disulfide (DADS) imparted hepatoprotection against alcohol induced fatty liver in C57BL/6 mice using microarray-based global gene expression analysis. Alcohol liquid diet resulted in severe fatty liver with increased levels of serum aspartate aminotransferease and alanine aminotransferease as well as triglycerides and decreased levels of liver glutathione and antioxidant enzymes. The major canonical pathways implicated by alcohol treatment are the metabolisms of xenobiotics by cytochrome P450, glutathione, and arachidonic acid. Treatment with DADS or GO normalized the serum aminotransferease levels and liver antioxidant enzymes and reduced the contents of triglycerides and cholesterol. The canonical pathways involved in the amelioration of liver include arachidonic acid metabolism, altered T cell and B cell signaling, tryptophan metabolism, antigen presentation pathway for DADS, metabolism of xenobiotics, mitotic roles of Polo-like kinase, fatty acid metabolism, LPS/IL-1 mediated inhibition of RXR function, and C21-steroid hormone metabolism for GO.
Insights
Garlic oil (GO) and diallyl disulfide (DADS) protect against alcohol-induced fatty liver by restoring liver enzymes and reducing harmful fats. These compounds modulate key metabolic pathways, offering a potential therapeutic strategy for alcoholic fatty liver disease.
Area of Science:
- Hepatology
- Molecular Biology
- Nutritional Science
Background:
- Alcohol abuse is a leading cause of fatty liver disease, contributing significantly to global morbidity and mortality.
- Garlic and its compounds have demonstrated potential hepatoprotective effects in previous studies.
- Understanding the molecular mechanisms underlying garlic's protective action against alcoholic fatty liver is crucial for therapeutic development.
Purpose of the Study:
- To investigate the molecular mechanisms by which garlic oil (GO) and diallyl disulfide (DADS) protect against alcohol-induced fatty liver in a mouse model.
- To identify the specific gene expression pathways modulated by GO and DADS in the context of alcoholic liver injury.
Main Methods:
- C57BL/6 mice were fed an alcohol liquid diet to induce fatty liver.
- Mice were treated with garlic oil (GO) or diallyl disulfide (DADS).
- Microarray-based global gene expression analysis was employed to assess molecular changes.
Main Results:
- Alcohol-induced fatty liver was characterized by elevated serum aminotransferases and triglycerides, and reduced liver glutathione and antioxidant enzymes.
- Treatment with DADS or GO normalized serum aminotransferase levels and improved liver antioxidant enzyme activity.
- DADS and GO treatments significantly reduced triglyceride and cholesterol content in the liver.
- Gene expression analysis revealed that DADS and GO modulated pathways including arachidonic acid metabolism, xenobiotic metabolism, and immune signaling.
Conclusions:
- Garlic oil (GO) and diallyl disulfide (DADS) exhibit significant hepatoprotective effects against alcohol-induced fatty liver in mice.
- These protective effects are mediated through the modulation of critical metabolic and signaling pathways.
- GO and DADS represent promising natural compounds for the prevention and treatment of alcoholic fatty liver disease.
