GSE109739
Adipose tissue mediate insulin resistance in obesity mice through the exosomal transfer of miR-141-3p into hepatocytes
Exosomes which are nano-vesicles and released from living cells, have attracted more attention as an important mediator for cell-to-cell communication. Given that obesity often causes insulin resistance, it is significant to test whether exosomes derived from obesity adipose tissue possess any capacity in regulating insulin sensitivity. In this study we purified exosomes from the adipose tissue. Exosomes derived from ob/ob mice (Ob-exosomes) and B6 mice fed a high-fat diet (HFD-exosomes) displayed similar size and molecular maker to those originated from the normal B6 mice (WT-exosomes), but their regulatory role in insulin sensitivity was opposite. Abundant exosomal miRNAs were detected by the Next Generation Sequencing. Ob-exosomes encapsulated the lower levels of miR-141-3p compared to WT-exosomes, furthermore, miR-141-3p can be effectively delivered into AML12 cells accompanied by the absorption of Ob-exosomes and WT-exosomes. But the absorption of miR-141-3p from adipose tissues to AML12 cells could be blocked by GW4869, an inhibitor of exosome biogenesis and release. Importantly, the exosomal miR-141-3p functionally down-regulated its target gene Pten expression in AML12 cells, and the knockdown of miR-141-3p inhibited the insulin response and glucose uptake in AML12 cells, however Ob-exosomes-mediated inhibitory effects on insulin function disappeared after overexpression of miR-141-3p. These data indicate that the absorption of exosomes released from obesity adipose tissue including lower level of miR-141-3p than healthy adipose tissue into hepatocytes can significantly inhibit the insulin sensitivity and glucose uptake. Thus, our study may certify a novel mechanism that the secretion of “harmful” exosomes from obesity adipose tissues cause insulin resistance. Overall design: exosomal miRNA profiles of 4 month wild type (WT), ob/ob, HFD mice adipose tissue were generated by high throughout sequencing, using illumina HiSeqTM2500.