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Resveratrol Alleviates Skeletal Muscle Insulin Resistance by Downregulating Long Noncoding RNA

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 ex...

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Autores principales: Liu, Zhihong, Zhang, Zhimei, Song, Guangyao, Wang, Xing, Xing, Hanying, Wang, Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791716/
https://www.ncbi.nlm.nih.gov/pubmed/35096054
http://dx.doi.org/10.1155/2022/2539519
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author Liu, Zhihong
Zhang, Zhimei
Song, Guangyao
Wang, Xing
Xing, Hanying
Wang, Chao
author_facet Liu, Zhihong
Zhang, Zhimei
Song, Guangyao
Wang, Xing
Xing, Hanying
Wang, Chao
author_sort Liu, Zhihong
collection PubMed
description 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.
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spelling pubmed-87917162022-01-27 Resveratrol Alleviates Skeletal Muscle Insulin Resistance by Downregulating Long Noncoding RNA Liu, Zhihong Zhang, Zhimei Song, Guangyao Wang, Xing Xing, Hanying Wang, Chao Int J Endocrinol Research Article 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. Hindawi 2022-01-19 /pmc/articles/PMC8791716/ /pubmed/35096054 http://dx.doi.org/10.1155/2022/2539519 Text en Copyright © 2022 Zhihong Liu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Zhihong
Zhang, Zhimei
Song, Guangyao
Wang, Xing
Xing, Hanying
Wang, Chao
Resveratrol Alleviates Skeletal Muscle Insulin Resistance by Downregulating Long Noncoding RNA
title Resveratrol Alleviates Skeletal Muscle Insulin Resistance by Downregulating Long Noncoding RNA
title_full Resveratrol Alleviates Skeletal Muscle Insulin Resistance by Downregulating Long Noncoding RNA
title_fullStr Resveratrol Alleviates Skeletal Muscle Insulin Resistance by Downregulating Long Noncoding RNA
title_full_unstemmed Resveratrol Alleviates Skeletal Muscle Insulin Resistance by Downregulating Long Noncoding RNA
title_short Resveratrol Alleviates Skeletal Muscle Insulin Resistance by Downregulating Long Noncoding RNA
title_sort resveratrol alleviates skeletal muscle insulin resistance by downregulating long noncoding rna
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791716/
https://www.ncbi.nlm.nih.gov/pubmed/35096054
http://dx.doi.org/10.1155/2022/2539519
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