Resveratrol improves skeletal muscle insulin resistance through downregulating lncRNA NONMMUT044897.2

Abstract

Background: Long non-coding RNA (lncRNA) has proved to be crucial factors in the progression of insulin resistance (IR). Resveratrol (RSV) exhibits promising therapeutic potential for the IR. Nonetheless, whether RSV could influence the expression of lncRNAs and the interaction mechanisms in IR remain unclear.Methods: We conducted high-throughput sequencing to detect the lncRNAs and mRNAs expression signatures and the co-expression network of lncRNAs and mRNAs in skeletal muscle after a high-fat diet (HFD)-induced IR mice model with or without RSV treatment, including hierarchical clustering, gene enrichment and gene co-expression networks analysis. Highly differentially expressed lncRNAs were selected and validated by RT-qPCR. Finally, the biological functions of the selected lncRNAs were investigated by silencing expressing the target genes through lentivirus transfection in C2C12 mouse myotubes cells.Results: We revealed that 338 mRNAs and 629 lncRNAs whose expression in skeletal muscle after a high-fat diet (HFD)-induced IR mice model was reversed by RSV treatment. Gene Ontology and Kyoto encyclopedia of genes and genomes databases indicated that the differential expression mRNAs modulate the insulin signaling pathway. After validating randomly selected lncRNAs via RT-qPCR, we found that lncRNA (NONMMUT044897.2) and Suppressor of Cytokine Signaling 1 (SOCS1) were up-regulated in the HFD group, and reversed by RSV treatment. Additionally, NONMMUT044897.2 was validated to function as a ceRNA of microRNA (miR)-7051-5p and SOCS1 was confirmed as a target for miR‑7051-5p. We further performed lentivirus transfection to knockdown NONMMUT044897.2 in vitro and found that NONMMUT044897.2 silence inactivated SOCS1 and promoted the insulin signaling pathway. Importantly, RSV could mimic the effects of silencing NONMMUT044897.2.Conclusion: Our study revealed that resveratrol improves skeletal muscle IR might be via regulation of NONMUT044897.2.

Resveratrol Alleviates Skeletal Muscle Insulin Resistance by Downregulating Long Noncoding RNA

“…Blood glucose was detected on the tail vein with a glucose meter at 0, 15, 30, 60, and 120 min after injection. The IR model was validated by determining the area under the curve in accordance with the protocol presented in our previously published study [ 29 ]. Animal studies (2019E369) were approved by the ethics committee of the Hebei General Hospital, and all animal experimental procedures complied with the National Institutes of Health guide for the care and use of laboratory animals.…”