Liraglutide alleviates diabetic cardiomyopathy in streptozotocin-induced diabetic rats by enhancing mitophagy mediated by the AMPK-Parkin signaling pathway

doi:10.4239/wjd.v16.i12.112423

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 16, Issue 12

This Article

Academic Content and Language Evaluation of This Article

CrossCheck and Google Search of This Article

Academic Rules and Norms of This Article

Supplementary Materials of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Number of Hits and Downloads for This Article

Total Article Views (0)

All Articles published online

The chart showing PDF series, HTML series, Figures (1-7) series.

Item

Count

PDF

HTML

Figures (1-7)

Sum=20

Featured Article

The chart showing Browse series, Download series.

Item

Count

Browse

Download

Sum=45

Publishing Process of This Article

Item

Count

Browse

Download

Sum=2

Dec 15, 2025 (publication date) through Dec 15, 2025

Times Cited of This Article

Times Cited (0)

Journal Information of This Article

Publication Name

World Journal of Diabetes

ISSN

1948-9358

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Diabetes. Dec 15, 2025; 16(12): 112423
Published online Dec 15, 2025. doi: 10.4239/wjd.v16.i12.112423

Liraglutide alleviates diabetic cardiomyopathy in streptozotocin-induced diabetic rats by enhancing mitophagy mediated by the AMPK-Parkin signaling pathway

Ya-Xin Zhu, Wei Zhang, Hui-Lin Qu, Yue Zhang, Ruo-Qian Zhou, Ping Li, Fang Wang, Yan Zhang, Hui-Hui Liu, Sha Li, Qian Dong, Ke-Fei Dou, Yuan-Lin Guo, Jian-Jun Li, Rui-Xia Xu

Ya-Xin Zhu, Wei Zhang, Hui-Lin Qu, Yue Zhang, Ruo-Qian Zhou, Ping Li, Fang Wang, Yan Zhang, Hui-Hui Liu, Sha Li, Qian Dong, Ke-Fei Dou, Yuan-Lin Guo, Jian-Jun Li, Rui-Xia Xu, Cardiometabolic Medicine Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China

Co-first authors: Ya-Xin Zhu and Wei Zhang.

Co-corresponding authors: Jian-Jun Li and Rui-Xia Xu.

Author contributions: Zhu YX and Zhang W contribute equally to this study as co-first authors; Li JJ and Xu RX contribute equally to this study as co-corresponding authors; Zhu YX, Zhang W, Qu HL and Zhang Y contributed equally to the performance of the experiments, drafting the manuscript, analyzing the data and producing the figures; Zhou RQ and Zhang Y performed the literature research and statistical analysis; Liu HH, Li S and Dong Q contributed new reagents and analytic tools; Li P, Wang F and Dou KF provided clinical insights and supervised the writing of the written text; Guo YL, Li JJ and Xu RX conceptualized and designed the study; all authors have read and approved the final manuscript.

Supported by National Natural Science Foundation of China, No. 81370221 and No. 82172334; PUMC Youth Fund, No. 3332018200; National Science and Technology Major Project of the Ministry of Science and Technology of China, No. 2024ZD0522005; and CAMS Innovation Fund for Medical Science, No. 2016-CXGC05-4 and No. 2021-I2M-1-008.

Institutional animal care and use committee statement: The animal feeding and animal experiments of this project strictly follow the experimental animal welfare policy. All experimental operations and experimental inspections are carried out after the use of isoflurane. The researchers do their best to reduce and eliminate the fear and pain of experimental animals. The Sino Animal (Beijing) Science and Technology Development Co., Ltd approved the animal experimental research project (No. 20240234YZH-3R).

Conflict-of-interest statement: The authors declare that they have no conflict of interest.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: No additional data are available.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Rui-Xia Xu, PhD, Cardiometabolic Medicine Center, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing 100037, China. ruixiaxu@sina.com

Received: August 11, 2025
Revised: September 28, 2025
Accepted: November 12, 2025
Published online: December 15, 2025
Processing time: 128 Days and 17.1 Hours

Abstract

BACKGROUND

Recent studies have shown that liraglutide, a glucagon-like peptide-1 receptor agonist, has unexpected cardioprotective effects. However, the distinctive effects of liraglutide on diabetic cardiomyopathy (DCM), particularly its effect on mitophagy, have not been fully elucidated.

AIM

To investigate the effects of liraglutide on cardiac damage and mitophagy in DCM rats.

METHODS

A high-fat diet and streptozotocin were used to induce DCM in rats. After 12 weeks of liraglutide treatment, rats underwent assessments of cardiac function, serum biochemical parameters, histological changes, apoptosis index, and protein levels. Furthermore, neonatal rat cardiomyocytes (NRCMs) were exposed to 25 mmol/L glucose plus 250 μmol/L palmitate (high glucose + palmitic acid), with or without 200 nmol/L liraglutide, to investigate the effects of liraglutide on cardiomyocyte injury and the underlying mechanisms.

RESULTS

Liraglutide improved myocardial function and ameliorated cardiac damage in DCM rats, as indicated by reduced myocardial apoptosis, hypertrophy, and interstitial fibrosis (P < 0.05). In NRCMs, Liraglutide alleviated mitochondrial morphological and functional damage as well as oxidative stress, improved mitophagic defects, and reduced cell apoptosis (P < 0.05). Mechanistically, liraglutide alleviated NRCMs damage by enhancing mitophagy mediated by the adenosine monophosphate-activated protein kinase (AMPK)-Parkin signaling pathway, which was evidenced by the reversal of its effects upon compound C treatment.

CONCLUSION

Liraglutide exerted cardioprotective effects in DCM rats by inhibiting cardiomyocyte apoptosis and promoting mitophagy mediated by the AMPK-Parkin signaling pathway.

Keywords: Diabetic cardiomyopathy; Liraglutide; Apoptosis; Mitochondria; Mitophagy; Parkin; AMPK signaling pathway

Core Tip: This study investigates the cardioprotective effects of liraglutide, a glucagon-like peptide-1 receptor agonist, in a rat model of diabetic cardiomyopathy (DCM) and in neonatal rat cardiomyocytes exposed to high glucose and palmitate. Liraglutide significantly improved cardiac function, alleviated cardiac damage—reducing myocardial apoptosis, hypertrophy, and interstitial fibrosis, and inhibited cardiomyocyte apoptosis by restoring mitochondrial function and promoting mitophagy through activation of the adenosine monophosphate-activated protein kinase-Parkin signaling pathway. These findings provide insight into the role of liraglutide in DCM and support its potential as a therapeutic strategy to mitigate cardiac injury in DCM.