ISSN: 1449-2288International Journal of Biological Sciences
Global reach, higher impact
Int J Biol Sci 2019; 15(2):351-368. doi:10.7150/ijbs.28522 This issue Cite
Research Paper
Exosomal transfer of obesity adipose tissue for decreased miR-141-3p mediate insulin resistance of hepatocytes
1. Institute of Biomedicine, Department of Cellular Biology, Jinan University
2. National engineering research center of genetic Medicine, Key laboratory of Bioengineering Medicine of Guangdong Province, Jinan University
3. Department of Biotechnology, Jinan University
# These authors contributed equally to this work
Abstract
Exosomes, the nano-vesicles released from living cells, were the important mediator for cell-to-cell communication. In order to clarify whether the exosomes derived from obesity adipose tissue mediate insulin resistance of hepatocytes, we extract the exosomes from the adipose tissue of different mice models. Exosomes derived from ob/ob mice (Ob-exosomes), B6 mice fed with a high-fat diet (HFD-exosomes) and normal B6 mice (WT-exosomes) displayed similar size and molecular makers, but their effect on the insulin sensitivity of hepatocytes were obviously different or opposite. Abundant exosomal miRNAs in Ob-, HFD- and WT-exosomes were detected by the Next Generation Sequencing. The levels of miR-141-3p in Ob- and HFD-exosomes were significantly lower than WT-exosomes. MiR-141-3p can be effectively delivered into AML12 cells accompanied by the absorption of exosomes, but the absorption of miR-141-3p into AML12 cells could be blocked by GW4869, an inhibitor of exosome biogenesis and release. Importantly, the Ob-exosomes or miR-141-3p knockdown in WT--exosomes obviously inhibited the insulin response and glucose uptake of AML12 cells, however, the inhibitory effects on insulin function disappeared after the overexpression of miR-141-3p in Ob-exosomes or AML12 cells. The effects of miR-141-3p on insulin function could be achieved by improving the level of phosphorylation of AKT and enhancing insulin signal transduction. Therefore, the absorption of hepatocytes for exosomes released from obesity adipose tissue containing less miR-141-3p than healthy adipose tissue can significantly inhibit the insulin sensitivity and glucose uptake. Our study may certify a novel mechanism that the secretion of “harmful” exosomes from obesity adipose tissues cause insulin resistance.
Keywords: obesity, insulin resistance, exosomes, miR-141-3p, hepatocytes
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