Neuregulin-4 attenuates diabetic cardiomyopathy by regulating autophagy via the AMPK/mTOR signalling pathway
- Cardiovasc Diabetol. 2022 Oct 11;21(1):205. doi: 10.1186/s12933-022-01643-0.
- 1. Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Heping West Road No. 215, Shijiazhuang, 050000, China.
- 2. Department of Cardiology, Shijiazhuang Great Wall Hospital of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, 050000, China.
- 3. Department of Cardiovascular Medicine, The Second Hospital of Hebei Medical University, Heping West Road No. 215, Shijiazhuang, 050000, China. [email protected].
- 4. Hebei Key Laboratory of Laboratory Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China. [email protected].
Background: Diabetic cardiomyopathy is characterized by left ventricle dysfunction, cardiomyocyte Apoptosis, and interstitial fibrosis and is a serious complication of diabetes mellitus (DM). Autophagy is a mechanism that is essential for maintaining normal heart morphology and function, and its dysregulation can produce pathological effects on diabetic hearts. Neuregulin-4 (Nrg4) is an adipokine that exerts protective effects against metabolic disorders and Insulin resistance. The aim of this study was to explore whether Nrg4 could ameliorate DM-induced myocardial injury by regulating Autophagy.
Methods: Four weeks after the establishment of a model of type 1 diabetes in mice, the mice received Nrg4 treatment (with or without an Autophagy inhibitor) for another 4 weeks. The cardiac functions, histological structures and cardiomyocyte Apoptosis were investigated. Autophagy-related protein levels along with related signalling pathways that regulate Autophagy were evaluated. In addition, the effects of Nrg4 on Autophagy were also determined in cultured primary cardiomyocytes.
Results: Nrg4 alleviated myocardial injury both in vivo and in vitro. The Autophagy level was decreased in type 1 diabetic mice, and Nrg4 intervention reactivated Autophagy. Furthermore, Nrg4 intervention was found to activate Autophagy via the AMPK/mTOR signalling pathway. Moreover, when Autophagy was suppressed or the AMPK/mTOR pathway was inhibited, the beneficial effects of Nrg4 were diminished.
Conclusion: Nrg4 intervention attenuated diabetic cardiomyopathy by promoting Autophagy in type 1 diabetic mice. Additionally, Nrg4 induced Autophagy via the AMPK/mTOR signalling pathway.