Skeletal muscle insulin resistance induced by a high-fat diet has been implicated in the development of type 2 diabetes. However, the precise molecular mechanisms involved are only partially understood. Recently, studies have shown that microRNAs play an important role in insulin resistance in various tissues. In this study, microRNA expression profiles of skeletal muscle of mice fed a high-fat or normal diet were analyzed using microarrays and the results were confirmed by real-time reverse-transcription polymerase chain reaction. Gene Ontology (GO) and pathway mapping tools were employed to analyze systemically the biological processes and signaling pathways affected by the differential expression of microRNAs. In this study, we show that 30 microRNAs are differentially expressed between 2 groups of mice. Compared to the mice fed a normal diet, there were 8 microRNAs up-regulated and 22 microRNAs down-regulated in the high-fat diet-fed mice. Furthermore, we confirm that the MAPK signaling pathway highlighted in this study is involved in skeletal muscle insulin resistance. These results indicate that skeletal muscle insulin resistance induced by a high-fat diet is associated with a group of microRNAs. GO and pathway mapping are a valid and effective approach for analyzing the function of microRNAs and the results could be a guideline for further investigation.

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