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Open Access 01-12-2024 | Diabetic Cardiomyopathy | Research

Irisin attenuates type 1 diabetic cardiomyopathy by anti-ferroptosis via SIRT1-mediated deacetylation of p53

Authors: Yuan-juan Tang, Zhen Zhang, Tong Yan, Ken Chen, Guo-fan Xu, Shi-qiang Xiong, Dai-qian Wu, Jie Chen, Pedro A. Jose, Chun-yu Zeng, Jin-juan Fu

Published in: Cardiovascular Diabetology | Issue 1/2024

Abstract

Background

Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia–reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known.

Methods and results

T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose.

Conclusion

This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.

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Title: Irisin attenuates type 1 diabetic cardiomyopathy by anti-ferroptosis via SIRT1-mediated deacetylation of p53
Authors: Yuan-juan Tang
Zhen Zhang
Tong Yan
Ken Chen
Guo-fan Xu
Shi-qiang Xiong
Dai-qian Wu
Jie Chen
Pedro A. Jose
Chun-yu Zeng
Jin-juan Fu
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Diabetic Cardiomyopathy
Published in: Cardiovascular Diabetology / Issue 1/2024
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/s12933-024-02183-5

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