MicroRNA expression profile in Lieber-DeCarli diet-induced alcoholic and methionine choline deficient diet-induced nonalcoholic steatohepatitis models in mice.
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 TNFalpha, 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.
Dolganiuc
Angela
A
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605-2324, USA.
Petrasek
Jan
J
Kodys
Karen
K
Catalano
Donna
D
Mandrekar
Pranoti
P
Velayudham
Arumugam
A
Szabo
Gyongyi
G
D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002796:Choline Deficiency / Q000235:genetics* / Q000473:pathology*; D016207:Cytokines / Q000097:blood; D004032:Diet; D000431:Ethanol / Q000633:toxicity*; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology; D005235:Fatty Liver, Alcoholic / Q000235:genetics* / Q000473:pathology; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008715:Methionine / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics*
D002492:Central Nervous System Depressants; D016207:Cytokines; D035683:MicroRNAs; D000431:Ethanol; D008715:Methionine