MicroRNA Expression Profile in Lieber-DeCarli Diet-Induced Alcoholic and Methionine Choline Deficient Diet-Induced Nonalcoholic Steatohepatitis Models in Mice
Version of Record online: 1 JUL 2009
Copyright © 2009 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 33, Issue 10, pages 1704–1710, October 2009
How to Cite
Dolganiuc, A., Petrasek, J., Kodys, K., Catalano, D., Mandrekar, P., Velayudham, A. and Szabo, G. (2009), MicroRNA Expression Profile in Lieber-DeCarli Diet-Induced Alcoholic and Methionine Choline Deficient Diet-Induced Nonalcoholic Steatohepatitis Models in Mice. Alcoholism: Clinical and Experimental Research, 33: 1704–1710. doi: 10.1111/j.1530-0277.2009.01007.x
- Issue online: 24 SEP 2009
- Version of Record online: 1 JUL 2009
- Received for publication November 26, 2008; accepted May 1, 2009.
- In Vivo
Background: Alcoholic and nonalcoholic steatohepatitis are leading causes of liver diseases worldwide. While of different etiology, these share common pathophysiological mechanisms and feature abnormal fat metabolism, inflammation and fibrosis. MicroRNAs (miRNA) are highly conserved noncoding RNAs that control gene expression at the post-transcriptional level either via the degradation of target mRNAs or the inhibition of translation. Each miRNA controls the expression of multiple targets; miRNAs have been linked to regulation of lipid metabolism and inflammation.
Methods: We fed Lieber-DeCarli alcohol or methionine-choline-deficient (MCD) diets to C57Bl6 and analyzed livers for histopathology, cytokines by ELISA, alanine aminotransferase (ALT) by biochemical assay, and microRNA profile by microarray.
Results: Both Lieber-DeCarli and MCD diets lead to development of liver steatosis, liver injury, indicated by increased ALT, and elevated levels of serum TNFα, suggesting that animal models portray the pathophysiological features of alcoholic and nonalcoholic fatty liver, respectively. We identified that Lieber-deCarli diet up-regulated 1% and down-regulated 1% of known miRNA; MCD diet up-regulated 3% and down-regulated 1% of known miRNA, compared to controls. Of miRNAs that changed expression levels, 5 miRNAs were common in alcoholic and nonalcoholic fatty livers: the expression of both miR-705 and miR-1224 was increased after Lieber-DeCarli or MCD diet feeding. In contrast, miR-182, miR-183, and miR-199a-3p were down-regulated in Lieber-deCarli feeding, while MCD diet lead to their up-regulation, compared to corresponding controls.
Conclusions: Our findings indicate etiology-specific changes in miRNA expression profile during steatohepatitis models, which opens new avenues for research in the pathophysiology of alcoholic and nonalcoholic fatty liver disease.