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

Content Provider	Springer Nature : BioMed Central
Author	Tang, Yuan-juan Zhang, Zhen Yan, Tong Chen, Ken Xu, Guo-fan Xiong, Shi-qiang Wu, Dai-qian Chen, Jie Jose, Pedro A. Zeng, Chun-yu Fu, Jin-juan
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.
Related Links	https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-024-02183-5.pdf
Ending Page	19
Page Count	19
Starting Page	1
File Format	HTM / HTML
ISSN	14752840
DOI	10.1186/s12933-024-02183-5
Journal	Cardiovascular Diabetology
Issue Number	1
Volume Number	23
Language	English
Publisher	BioMed Central
Publisher Date	2024-04-02
Access Restriction	Open
Subject Keyword	Diabetes Angiology Cardiology Type 1 diabetic cardiomyopathy Ferroptosis Irisin p53 SIRT1
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Internal Medicine Endocrinology, Diabetes and Metabolism
Journal Impact Factor	8.5/2023
5-Year Journal Impact Factor	8.9/2023

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