Plasma microRNA expression profile in mice with high fat diet-induced insulin resistance and its relationship with TLR4
10.3969/j.issn.1000-484X.2016.12.004
- VernacularTitle:高脂饮食诱导胰岛素抵抗小鼠血浆 microRNA表达谱及其与 TLR4的关系
- Author:
Ke MA
;
Xiaobo ZHU
;
Zhiwei XU
;
Xiaotong CHANG
- Keywords:
High fat diet;
Insulin resistance;
Toll like receptor 4;
miRNAs expression profile
- From:
Chinese Journal of Immunology
2016;32(12):1745-1752
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To screen the plasma microRNAs( miRNAs) of differential expression in a high fat diet-induced insulin resistance in mouse models;further investigations on the mice with insulin resistance treated by TLR4 inhibitors TAK-242,and to study the changes of plasma miRNAs expression profile and the relationship among TLR4, miRNAs and high fat diet-induced insulin resistance. Methods:The plasma samples were from 3 mouse groups of previous study,namely,the control group with general basic diet ( low fat diet,LFD) ,TLR4 inhibitors TAK-242 treatment group with a high fat diet ( HFD-T) and the high fat diet control group( HFD-C) . The differential expressed miRNAs was screened by expression profiling of plasma miRNAs, which was detected using mouse miRNA microarray. The quantitative Real-Time PCR ( qRT-PCR ) was used to verify the results of microarray. The target genes of differential expressed miRNAs were predicted in TLR4 signaling pathway using bioinformatics methods,and the GO and KEGG database molecular annotation system were used to investigate the main effects of the miRNAs targeted genes on the biological functions or signal pathway. Results:The screening results of miRNA microarray chip showed that,comparing miRNAs expression between HFD group and LFD control group,185 miRNAs were significant in the high fat diet group,including 6 up-regulated and 179 down-regulated miRANs. A significant difference of miRANs was also found between HFD-T group and LFD control group,the total number of differential expression miRNAs was 171,and all of them were down-regulated. Comparing miRNAs expression between HFD-C group and HFD-T group,13
miRNAs were significant in HFD-T group,all of them were down-regulated. Bioinformatics analysis results showed that a total of 10 in-teraction proteins with TLR4 were predicted;the difference of mmu-miR-3095-3p,mmu-miR-5113,mmu-miR-709 and mmu-miR-335-3p expression levels was more than 1 000 times between HFD-C group and HFD-T group,and their target genes can be found in TLR4-in-teraction protein or Toll like receptor signaling pathway;GO and KEGG analysis showed 74% of these target genes belonged to the biological processes genes, and the transcription factors accounted for 82%. The expression of mmu-miR-3095-3p, mmu-miR-5113, mmu-miR-709 and mmu-miR-335-3p detected by qRT-PCR exhibited the similar patterns of down regulation to those shown in microarray results. Conclusion:When insulin resistance occurs,there is a change in plasma miRNAs expression profile,this change is associated with TLR4 and its signaling pathways. The finding enrichs the possible mechanisms of insulin resistance and provides a basis for finding miRNAs diagnostic markers for early diagnosis of insulin resistance.
