https://scholars.lib.ntu.edu.tw/handle/123456789/641768
Title: | Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance | Authors: | Hsu, Man-Chen Chen, Chia-Hui Wang, Mu-Chun Chen, Wen-Hua Hu, Po-An Guo, Bei-Chia Chang, Ru-Wen Wang, Chih-Hsien TZONG-SHYUAN LEE |
Keywords: | CK2α; apigenin; fetuin-A; insulin receptor; insulin resistance | Issue Date: | 2024 | Journal Volume: | 20 | Journal Issue: | 5 | Source: | International journal of biological sciences | Abstract: | Fetuin-A, a hepatokine secreted by hepatocytes, binds to insulin receptors and consequently impairs the activation of the insulin signaling pathway, leading to insulin resistance. Apigenin, a flavonoid isolated from plants, has beneficial effects on insulin resistance; however, its regulatory mechanisms are not fully understood. In the present study, we investigated the molecular mechanisms underlying the protective effects of apigenin on insulin resistance. In Huh7 cells, treatment with apigenin decreased the mRNA expression of fetuin-A by decreasing reactive oxygen species-mediated casein kinase 2α (CK2α)-nuclear factor kappa-light-chain-enhancer of activated B activation; besides, apigenin decreased the levels of CK2α-dependent fetuin-A phosphorylation and thus promoted fetuin-A degradation through the autophagic pathway, resulting in a decrease in the protein levels of fetuin-A. Moreover, apigenin prevented the formation of the fetuin-A-insulin receptor (IR) complex and thereby rescued the PA-induced impairment of the insulin signaling pathway, as evidenced by increased phosphorylation of IR substrate-1 and Akt, and translocation of glucose transporter 2 from the cytosol to the plasma membrane. Similar results were observed in the liver of HFD-fed mice treated with apigenin. Collectively, our findings revealed that apigenin ameliorates obesity-induced insulin resistance in the liver by targeting fetuin-A. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/641768 | ISSN: | 14492288 | DOI: | 10.7150/ijbs.91695 |
Appears in Collections: | 生理學科所 |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.