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Int J Biol Sci 2024; 20(5):1563-1577. doi:10.7150/ijbs.91695 This issue Cite

Research Paper

Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance

Man-Chen Hsu1, Chia-Hui Chen1, Mu-Chun Wang2, Wen-Hua Chen1, Po-An Hu1, Bei-Chia Guo1, Ru-Wen Chang3, Chih-Hsien Wang3✉, Tzong-Shyuan Lee1✉

1. Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
2. Department of Cardiovascular Surgery, Min-Sheng General Hospital, Taoyuan, Taiwan.
3. Cardiovascular Surgery, Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei 10051, Taiwan.

✉ Corresponding authors: Dr. Tzong-Shyuan Lee, DVM, Ph.D., Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan; Tel: +886-2-23123456, ext. 88242; Fax: +886-2-2396-4350, E-mail: ntutsle More

Citation:
Hsu MC, Chen CH, Wang MC, Chen WH, Hu PA, Guo BC, Chang RW, Wang CH, Lee TS. Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance. Int J Biol Sci 2024; 20(5):1563-1577. doi:10.7150/ijbs.91695. https://www.ijbs.com/v20p1563.htm
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Abstract

Graphic 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.

Keywords: apigenin, fetuin-A, CK2α, insulin receptor, insulin resistance

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APA
Hsu, M.C., Chen, C.H., Wang, M.C., Chen, W.H., Hu, P.A., Guo, B.C., Chang, R.W., Wang, C.H., Lee, T.S. (2024). Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance. International Journal of Biological Sciences, 20(5), 1563-1577. https://doi.org/10.7150/ijbs.91695.

ACS
Hsu, M.C.; Chen, C.H.; Wang, M.C.; Chen, W.H.; Hu, P.A.; Guo, B.C.; Chang, R.W.; Wang, C.H.; Lee, T.S. Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance. Int. J. Biol. Sci. 2024, 20 (5), 1563-1577. DOI: 10.7150/ijbs.91695.

NLM
Hsu MC, Chen CH, Wang MC, Chen WH, Hu PA, Guo BC, Chang RW, Wang CH, Lee TS. Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance. Int J Biol Sci 2024; 20(5):1563-1577. doi:10.7150/ijbs.91695. https://www.ijbs.com/v20p1563.htm

CSE
Hsu MC, Chen CH, Wang MC, Chen WH, Hu PA, Guo BC, Chang RW, Wang CH, Lee TS. 2024. Apigenin targets fetuin-A to ameliorate obesity-induced insulin resistance. Int J Biol Sci. 20(5):1563-1577.

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