Open Access

Metformin improves high‑fat diet‑induced insulin resistance in mice by downregulating the expression of long noncoding RNA NONMMUT031874.2

  • Authors:
    • Zhi-Mei Zhang
    • Zhi-Hong Liu
    • Qian Nie
    • Xue-Mei Zhang
    • Li-Qun Yang
    • Chao Wang
    • Lin-Lin Yang
    • Guang-Yao Song
  • View Affiliations

  • Published online on: March 16, 2022     https://doi.org/10.3892/etm.2022.11261
  • Article Number: 332
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Metformin (MET) is the first‑line therapeutic option for patients with type 2 diabetes that has garnered substantial attention over recent years. However, an insufficient number of studies have been performed to assess its effects on insulin resistance and the expression profile of long noncoding RNAs (lncRNAs). The present study divided mice into three groups: Control group, high‑fat diet (HFD) group and HFD + MET group. A high‑throughput sequencing analysis was conducted to detect lncRNA and mRNA expression levels, and differentially expressed lncRNAs were selected. Subsequently, the differentially expressed lncRNAs were validated both in vivo and in vitro (mouse liver AML12 cells treated with Palmitic acid) models of insulin resistance. After validating randomly selected lncRNAs via reverse transcription‑quantitative PCR a novel lncRNA, NONMMUT031874.2, was identified, which was upregulated in the HFD group and reversed with MET treatment. To investigate the downstream mechanism of NONMMUT031874.2, lncRNA‑microRNA (miR/miRNA)‑mRNA co‑expression network was constructed and NONCODE, miRBase and TargetScan databases were used, which indicated that NONMMUT031874.2 may regulate suppressor of cytokine signaling 3 by miR‑7054‑5p. For the in vitro part of the present study, AML12 cells were transfected with small interfering RNA to knock down NONMMUT031874.2 expression before being treated with palmitic acid (PA) and MET. The results showed that the expression of NONMMUT031874.2 was significantly increased whereas miR‑7054‑5p expression was significantly decreased by PA treatment. By contrast, after knocking down NONMMUT031874.2 expression or treatment with MET, the aforementioned in vitro observations were reversed. In addition, it was also found that NONMMUT031874.2 knockdown and treatment with MET exerted similar effects in alleviating insulin resistance and whilst decreasing glucose concentration in AML12 cells. These results suggest that MET treatment can ameliorate insulin resistance by downregulating NONMMUT031874.2 expression.
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May-2022
Volume 23 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Copy and paste a formatted citation
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Spandidos Publications style
Zhang Z, Liu Z, Nie Q, Zhang X, Yang L, Wang C, Yang L and Song G: Metformin improves high‑fat diet‑induced insulin resistance in mice by downregulating the expression of long noncoding RNA NONMMUT031874.2. Exp Ther Med 23: 332, 2022
APA
Zhang, Z., Liu, Z., Nie, Q., Zhang, X., Yang, L., Wang, C. ... Song, G. (2022). Metformin improves high‑fat diet‑induced insulin resistance in mice by downregulating the expression of long noncoding RNA NONMMUT031874.2. Experimental and Therapeutic Medicine, 23, 332. https://doi.org/10.3892/etm.2022.11261
MLA
Zhang, Z., Liu, Z., Nie, Q., Zhang, X., Yang, L., Wang, C., Yang, L., Song, G."Metformin improves high‑fat diet‑induced insulin resistance in mice by downregulating the expression of long noncoding RNA NONMMUT031874.2". Experimental and Therapeutic Medicine 23.5 (2022): 332.
Chicago
Zhang, Z., Liu, Z., Nie, Q., Zhang, X., Yang, L., Wang, C., Yang, L., Song, G."Metformin improves high‑fat diet‑induced insulin resistance in mice by downregulating the expression of long noncoding RNA NONMMUT031874.2". Experimental and Therapeutic Medicine 23, no. 5 (2022): 332. https://doi.org/10.3892/etm.2022.11261