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Papers In Press, published online ahead of print September 1, 2009
J. Lipid Res., doi:10.1194/jlr.M800509-JLR200

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Journal of Lipid Research, Vol. 50, 1756-1765, September 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Differential expression of microRNAs in mouse liver under aberrant energy metabolic status^[S]

Shengjie Li^*, Xi Chen, Hongjie Zhang, Xiangying Liang, Yang Xiang, Chaohui Yu^*, Ke Zen^1,, Youming Li^1,* and Chen-Yu Zhang^1,

^* Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China

¹ To whom correspondence should be addressed. e-mail: dou900{at}163.com (Y.L.); cyzhang{at}nju.edu.cn (C-Y.Z.); kzen{at}nju.edu.cn (K.Z.)

Despite years of effort, exact pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains obscure. To gain an insight into the regulatory roles of microRNAs (miRNAs) in aberrant energy metabolic status and pathogenesis of NAFLD, we analyzed the expression of miRNAs in livers of ob/ob mice, streptozotocin (STZ)-induced type 1 diabetic mice, and normal C57BL/6 mice by miRNA microarray. Compared with normal C57BL/6 mice, ob/ob mice showed upregulation of eight miRNAs and downregulation of four miRNAs in fatty livers. Upregulation of miR-34a and downregulation of miR-122 was found in livers of STZ-induced diabetic mice. These results demonstrate that distinct miRNAs are strongly dysregulated in NAFLD and hyperglycemia. Comparison between miRNA expressions in livers of ob/ob mice and STZ-administered mice further revealed upregulation of four miRNAs and downregulation of two miRNAs in livers of ob/ob mice, indicating that these miRNAs may represent a molecular signature of NAFLD. A distinctive miRNA expression pattern was identified in ob/ob mouse liver, and hierarchical clustering of this pattern could clearly discriminate ob/ob mice from either normal C57BL/6 mice or STZ-administered mice. These findings suggest an important role of miRNAs in hepatic energy metabolism and implicate the participation of miRNAs in the pathophysiological processes of NAFLD.

Supplementary key words nonalcoholic fatty liver disease • energy metabolism • microarray • ob/ob mice

Abbreviations: FDR, false discovery rate; miRNA, microRNA; NAFLD, nonalcoholic fatty liver disease; qRT-PCR, quantitative reverse transcription polymerase chain reaction; SAM, significance analysis of microarray; STZ, streptozotocin

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