MiR-876-3p regulates glucose homeostasis and insulin sensitivity by targeting adiponectin

_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_miRNA_s 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.