miR-146a Overexpression Alleviated Inflammation and Insulin Resistance in High-Fat Diet Mice

Abstract: In this paper， the effect of exogenous miR-146a on high-fat diet-induced chronic inflammation and insulin resistance in mice was investigated. The mice models were fed with a high-fat diet (HFD， 45% calories from fat) for 18 weeks. The adenovirus products (30 μL) were injected into mice tail veins since the 5th week， which were carried out every 3-week for 5 total injections. Then glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were conducted for the mice model during the 17th and 18th weeks. After 18 weeks， serum， livers and epididymal adipose tissues were taken from mice models， followed by the measurements of inflammatory cytokine TNF-α and IL-6 in serum via enzyme-linked immunosorbent assay， the detection of miR-146a and CD68 expressions in liver and epididymal adipose tissue via Real-time PCR and immunohistochemical， and the analysis of Akt and p-AktSer473 protein level in liver before and after insulin stimulation via Western blot， respectively. As a result， the miR-146a level over expressed (P<0.05) while the CD68 expression decreased (P<0.01， P<0.001) in liver and epididymal adipose tissues via tail intravenous injection of miR-146a adenovirus expression vector， as compared to control group. Meanwhile， the contents of TNF-α and IL-6 in serum significantly reduced (P<0.05， P<0.01). Besides， the p-AktSer473 phosphorylation in liver up-regulated after insulin treated (P<0.05). Furthermore， GTT and ITT test results suggested that both glucose tolerance and insulin sensitivity improved (P<0.01， P<0.05) in this study. These results demonstrated that tail intravenous injection of miR-146a adenovirus expression vector could improve the expression level of miR-146a in vivo， thus alleviate chronic inflammation and insulin resistance.

CSTR: 32200.14.cjcb.2018.06.0009