Resveratrol Alleviates Skeletal Muscle Insulin Resistance by Downregulating Long Noncoding RNA

Zhihong Liu; Zhimei Zhang; Guangyao Song; Xing Wang; Hanying Xing; Chao Wang

doi:10.1155/2022/2539519

Resveratrol Alleviates Skeletal Muscle Insulin Resistance by Downregulating Long Noncoding RNA

Int J Endocrinol. 2022 Jan 19:2022:2539519. doi: 10.1155/2022/2539519. eCollection 2022.

Authors

Zhihong Liu^{1

2

3}, Zhimei Zhang^{1

2}, Guangyao Song^{1

2}, Xing Wang⁴, Hanying Xing⁴, Chao Wang⁴

Affiliations

¹ Department of Internal Medicine, Hebei Medical University, Shijiazhuang 050017, China.
² Endocrinology Department, Hebei General Hospital, Shijiazhuang 050051, China.
³ Endocrinology Department, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
⁴ Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang 050051, China.

Abstract

Long noncoding RNA (lncRNA) is a crucial factor in the progression of insulin resistance (IR). Resveratrol (RSV) exhibits promising therapeutic potential for IR. However, there are few studies on whether RSV improves IR through lncRNA. This study aimed to determine whether RSV could influence the expression of lncRNA and to elucidate the underlying mechanism. Mice were divided into three groups: control group, high-fat diet (HFD) group, and HFD + RSV group. We conducted a high-throughput sequencing analysis to detect lncRNA and mRNA expression signatures and the ceRNA-network in the skeletal muscles of mice that were fed an HFD to induce IR. Hierarchical clustering, gene enrichment, and gene ceRNA-network analyses were subsequently conducted. Differentially expressed lncRNAs were selected and validated via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The biological functions of the selected lncRNAs were investigated by silencing the target genes via lentivirus transfection of C2C12 mouse myotube cells. RSV treatment reversed the expression of 338 mRNAs and 629 lncRNAs in the skeletal muscles of mice with HFD-induced IR. The results of the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database analyses indicated that the differentially expressed mRNAs modulated type II diabetes mellitus. After validating randomly selected lncRNAs via RT-qPCR, we identified a novel lncRNA, NONMMUT044897.2, which was upregulated in the HFD group and reversed with RSV treatment. Additionally, NONMMUT044897.2 was proven to function as a ceRNA of microRNA- (miR-) 7051-5p. Suppressor of Cytokine Signaling 1 (SOCS1) was confirmed as a target of miR-7051-5p. We further performed lentivirus transfection to knock down NONMMUT044897.2 in vitro and found that NONMMUT044897.2 silenced SOCS1 and potentiated the insulin signaling pathway. Hence, RSV mimicked the silencing effect of lentivirus transfection on NONMMUT044897.2. Our study revealed that RSV reduced IR in mouse skeletal muscles via the regulation of NONMMUT044897.2.