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

Authors :
Hsu MC
Chen CH
Wang MC
Chen WH
Hu PA
Guo BC
Chang RW
Wang CH
Lee TS
Source :
International journal of biological sciences [Int J Biol Sci] 2024 Feb 11; Vol. 20 (5), pp. 1563-1577. Date of Electronic Publication: 2024 Feb 11 (Print Publication: 2024).
Publication Year :
2024

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.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)

Details

Language :
English
ISSN :
1449-2288
Volume :
20
Issue :
5
Database :
MEDLINE
Journal :
International journal of biological sciences
Publication Type :
Academic Journal
Accession number :
38481798
Full Text :
https://doi.org/10.7150/ijbs.91695