Abstract

BackgroundHepatic insulin resistance (IR) is an early pathological characteristic of many metabolic diseases, such as type 2 diabetes. Long noncoding RNAs (lncRNAs) have been identified as mediators of IR and related diseases. However, the roles of lncRNAs in hepatic IR remain largely unknown.MethodHigh-throughput sequencing was performed on ten liver tissue samples from five normal diet (ND)-fed mice and five high-fat diet (HFD)-induced hepatic IR mice, respectively. lncRNAs and mRNAs that were differentially expressed (DE) between the two groups were identified by bioinformatic analyses. Seven DE lncRNAs were validated by quantitative real-time PCR (q-PCR). The potential functions of the DE lncRNAs were predicted by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of target genes. In addition, integrated analysis was performed for the DE lncRNAs and mRNAs to predict their interaction relationships.ResultsA total of 232 DE lncRNAs were identified in the HFD-induced hepatic IR mice compared with the ND-fed mice. These DE lncRNAs included 108 upregulated and 124 downregulated lncRNAs, and 7 of the DE lncRNAs were validated by q-PCR. In addition, 291 DE mRNAs including 166 upregulated and 125 downregulated mRNAs were identified in the HFD group. Furthermore, target genes of the DE lncRNAs were predicted, and functional enrichment results showed that the enriched genes were involved in IR- and glycolipid metabolism-related processes. Additionally, the coexpression network was also constructed to further reflect the potential functions of the DE lncRNAs.ConclusionThe study describes the expression profiles of lncRNAs and mRNAs and the functional networks involved in HFD-induced hepatic IR. These findings may provide a new perspective for the study of lncRNAs in hepatic IR- and glycolipid metabolism-related diseases.

Highlights

  • Insulin resistance (IR) is considered to be associated with many metabolic disorders, such as type 2 diabetes and obesity

  • A total of 232 differentially expressed (DE) Long noncoding RNAs (lncRNAs) were identified in the high-fat diet (HFD)-induced hepatic insulin resistance (IR) mice compared with the normal diet (ND)-fed mice

  • These DE lncRNAs included 108 upregulated and 124 downregulated lncRNAs, and 7 of the DE lncRNAs were validated by quantitative real-time PCR (q-PCR)

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Summary

Introduction

Insulin resistance (IR) is considered to be associated with many metabolic disorders, such as type 2 diabetes and obesity. Insulin promotes anabolic metabolism in the liver by enhancing glucose consumption and lipid synthesis; the IR state is characterized by a failure to inhibit hepatic glucose production, with paradoxically increased fat accumulation, resulting in hyperglycemia and hypertriglyceridemia [1, 2]. Some reports have noted that lncRNAs play an important role in liver glycolipid metabolism. Zhu et al showed that the expression of the lncRNA MEG3 was increased in high-fat diet (HFD)-fed and ob/ob mice and upregulated by palmitate, oleate or linoleate. Hepatic insulin resistance (IR) is an early pathological characteristic of many metabolic diseases, such as type 2 diabetes. The roles of lncRNAs in hepatic IR remain largely unknown

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