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MiRNA-145 is involved in the development of resistin-induced insulin resistance in HepG2 cells
Fengyun Wen1, Yi Yang2, Dan Jin2
1Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, PR China; College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471003, Henan, PR China.
Background:
Resistin is associated with insulin resistance, and determining its developmental and molecular mechanisms may help the development of novel treatments. MicroRNAs (miRNAs) are involved in many physiological and pathological processes as negative regulators. However, it remains unclear whether miRNAs play a role in resistin-induced insulin resistance. We performed mouse liver miRNA microarrays to analyze the differences in expression between resistin-treated and control mice. Resistin upregulated miR-145 both in vivo and in vitro. Therefore, we aimed to study whether miR-145 played a role in resistin-induced insulin resistance.
Methods And Results:
We transfected HepG2 cells, and used miR-145 mimics and inhibitors to assess the role of miR-145 in resistin-induced insulin resistance. The overexpression of miR-145 inhibited glucose uptake in HepG2 cells, diminished the phosphorylation of Akt and IRS-1, and induced insulin resistance in hepatocytes. Next, a study of transcriptional regulation revealed that p65 was essential for the upregulation of miR-145 by resistin, and chromatin immunoprecipitation (ChIP) confirmed that p65 could bind to the promoter region of miR-145.
Conclusion:
miR-145 plays a role in the development of resistin-induced insulin resistance via the p65 pathway.
Insights
Resistin triggers microRNA-145 (miR-145) upregulation, promoting insulin resistance by inhibiting glucose uptake and key signaling proteins. This occurs through the p65 pathway, offering potential therapeutic targets.
Area of Science:
- Molecular Biology
- Endocrinology
- Metabolic Research
Background:
- Resistin is linked to insulin resistance, necessitating research into its mechanisms for novel treatment development.
- MicroRNAs (miRNAs) regulate gene expression, but their role in resistin-induced insulin resistance is not well understood.
- This study investigated the impact of resistin on miRNA expression in mouse liver tissue.
Purpose of the Study:
- To analyze miRNA expression differences in resistin-treated versus control mice.
- To determine if miR-145 plays a role in resistin-induced insulin resistance.
- To elucidate the molecular pathway involved in resistin's effect on miR-145.
Main Methods:
- Mouse liver miRNA microarrays were used to identify differentially expressed miRNAs.
- HepG2 cells were transfected with miR-145 mimics and inhibitors to assess functional effects.
- Transcriptional regulation and chromatin immunoprecipitation (ChIP) assays were performed to identify the regulatory pathway.
Main Results:
- Resistin upregulated miR-145 expression both in vivo and in vitro.
- Overexpression of miR-145 in HepG2 cells inhibited glucose uptake and diminished Akt and IRS-1 phosphorylation, inducing insulin resistance.
- The p65 pathway was identified as essential for resistin-induced miR-145 upregulation, with p65 binding to the miR-145 promoter region.
Conclusions:
- miR-145 is a key mediator in the development of resistin-induced insulin resistance.
- The p65 pathway is crucial for resistin's regulation of miR-145.
- Targeting the miR-145/p65 pathway may offer a novel therapeutic strategy for insulin resistance.
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