MiR-27a Promotes Insulin Resistance and Mediates Glucose Metabolism by Targeting PPAR-γ-Mediated PI3K/AKT Signaling
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This study aimed to establish a high-fat diet (HFD)-fed obese mouse model and a cell culture model of insulin resistance (IR) in mature 3T3-L1 adipocytes. A dual-luciferase reporter assay (DLRA) was confirmed interaction between miR-27a and the 3'-untranslated region (UTR) of Peroxisome proliferator-activated receptor (PPAR)-γ. The inhibition of PPAR-γ expression by microRNA (miR)-27a in IR cells at both the protein and mRNA levels was confirmed by a mechanistic investigation. Moreover, the 3'-UTR of PPAR-γ was found to be a direct target of miR-27a, based on the DLRA. Furthermore, antagomiR-27a upregulated the activation of PI3K/Akt signaling and glucose transporter type 4 (GLUT4) expression at the protein and mRNA levels. Additionally, the PPAR inhibitor T0070907 repressed the insulin sensitivity upregulated by antagomiR-27a, which was accompanied by the inhibition of PPAR-γ expression and increased levels of AKT phosphorylation and GLUT4. The PI3K inhibitor wortmannin reduced miR-27a-induced increases in AKT phosphorylation, glucose uptake, and GLUT4. miR-27a is considered to be involved in the PPAR-γ-PI3K/AKT-GLUT4 signaling axis, thus leading to increased glucose uptake and decreased IR in HFD-fed mice and 3T3-L1 adipocytes. Therefore, miR-27a is a novel target for the treatment of IR in obesity and diabetes.
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MicroRNAs located in exosomes of adipocytes and macrophages of adipose tissue and secreted into circulation can influence the development of insulin resistance through mechanisms such as inhibition of PPAR-gamma expression and affecting PI3K/AKT-GLUT4 signaling pathway.
“Studies show that these particles, located in exosomes of adipocytes and macrophages of adipose tissue and secreted from them into the circulation, can influence the development of IR through mechanisms, such as inhibition of peroxisome proliferator-activated receptor (PPAR-gamma) expression and affecting PI3K/AKT-GLUT4 signaling pathway [57,58,59].”
From The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome (2022) · cites this paper as [59]
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Bednarz, K., Kowalczyk, K., Cwynar, M., Czapla, D., Czarkowski, W., Kmita, D., Nowak, A., & Madej, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084334 · Cited by 148 · see citing works
- Authors
- Chen, T., Zhang, Y., Liu, Y., Zhu, D., Yu, J., Li, G., Sun, Z., Wang, W., Jiang, H., & Hong, Z.
- Affiliations
- Fujian Medical University (CN)
- First Affiliated Hospital of Henan University of Science and Technology (CN)
- Corresponding author
- Zhang, Yi
- Hong, Zhenzhen
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2019-09-28
- Volume
- 11
- Issue
- 18
- Pages
- 7510-7524
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC6781997
- OpenAlex
- W2976421607
- Cited by
- 134
- References
- 57
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 25 · 2023: 21 · 2022: 31 · 2021: 18 · 2020: 7
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Aging (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Fujian Province
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- miR-27a, insulin resistance, PPARγ, PI3K/Akt signaling, GLUT4, glucose uptake, glucose metabolism, obesity, high-fat diet, 3T3-L1 adipocytes, microRNA target regulation, T0070907, wortmannin, diabetes mellitus
- MeSH terms
- Animals, Gene Expression Regulation, Glucose, Insulin Resistance, Obesity, Up-Regulation, Phosphatidylinositol 3-Kinases, MicroRNAs, 3T3-L1 Cells, PPAR gamma, Proto-Oncogene Proteins c-akt, Mice, Diet, High-Fat
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