miRNA has been known to regulate diverse cellular and molecular functions. In the earlier study, we have reported that adipocytes differentiated from human mesenchymal stem cells (hMSC) on 72-h chronic insulin (CI) treatment exhibit insulin resistance (IR). Present study has further explored above model to investigate the role of early expressed miRNAs within human adipocytes to modulate differential adipokine expression as observed during IR. Our results highlight that miR-876-3p regulate glucose homeostasis and its dysregulation leads to IR. We found that miR-876-3p level is a critical determinant of adiponectin expression by virtue of its target within adiponectin 3′UTR. Regulatory effect of miR-876-3p impacts crosstalk between adiponectin and insulin signaling. Rosiglitazone treatment in CI-induced IR adipocytes drastically reduced miR-876-3p expression and increased adiponectin level. In line with this, lentiviral-mediated inhibition of miR-876-3p expression ameliorated CI and high-fat diet (HFD)-induced IR in adipocytes differentiated from hMSC and C57BL/6 mice, respectively. Our findings thus suggest that modulating miR-876-3p expression could provide novel opportunities for therapeutic intervention of obesity-associated metabolic syndrome.
Supplementary Table 1: 72 hours RNA-seq read data statistics. Each control and CI condition samples of 72 hours having three biological replicates. All replicates read data were quality assessment and control statistics given below in table.
Supplementary Table 2: 72 hours small RNA-seq read data statistics. Quality assessment and filtering reads statistic result of 72 hours small RNA-Seq data of adipose tissue having biological replicates.
File 1: Adipokine array coordinates and corresponding proteins.
File 2: Gene enrichment of validated miRNA target genes having significant Gene ontology tested by hyper-geometric test at 5% and bonferroni p-value adjustment. It included biological process and molecular function.