1. Academic Validation
  2. Neuregulin-4 attenuates diabetic cardiomyopathy by regulating autophagy via the AMPK/mTOR signalling pathway

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.
Hongchao Wang 1 Lijie Wang 1 Fuli Hu 2 Pengfei Wang 1 Yanan Xie 1 Fang Li 1 Bingyan Guo 3 4
Affiliations

Affiliations

  • 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. gbyan2008bs@163.com.
  • 4 Hebei Key Laboratory of Laboratory Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China. gbyan2008bs@163.com.
Abstract

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.

Keywords

Autophagy; Diabetic cardiomyopathy; Neuregulin-4; Signalling pathway.

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