MOTS-c and Exercise Restore Cardiac Function by Activating of NRG1-ErbB Signaling in Diabetic Rats.

Frontiers in endocrinology2022PMID: 35370955

View on PubMed DOI: 10.3389/fendo.2022.812032

Animal StudyMOTS-C

Plain Language Summary

Diabetic rat model study (HFD + STZ) with transcriptomic profiling demonstrating that both aerobic exercise and MOTS-c treatment reduce pathological cardiac remodeling and restore cardiac function in T2DM by activating the NRG1/ErbB signaling pathway—a cardioprotective pathway that promotes physiological myocardial adaptation and MOTS-c functions as an exercise mimetic by converging on the same signaling axis. Provides transcriptomic evidence for NRG1-ErbB as the shared molecular target. Establishes the transcriptomic basis for MOTS-c's exercise-mimetic cardiac protection in diabetes—demonstrating that both interventions normalize the same gene expression program, and identifying NRG1/ErbB as a druggable cardiac protective pathway activated by mitochondrial peptide signaling.

Abstract

Pathologic cardiac remodeling and dysfunction are the most common complications of type 2 diabetes. Physical exercise is important in inhibiting myocardial pathologic remodeling and restoring cardiac function in diabetes. The mitochondrial-derived peptide MOTS-c has exercise-like effects by improving insulin resistance, combatting hyperglycemia, and reducing lipid accumulation. We investigated the effects and transcriptomic profiling of MOTS-c and aerobic exercise on cardiac properties in a rat model of type 2 diabetes which was induced by feeding a high fat high sugar diet combined with an injection of a low dose of streptozotocin. Both aerobic exercise and MOTS-c treatment reduced abnormalities in cardiac structure and function. Transcriptomic function enrichment analysis revealed that MOTS-c had exercise-like effects on inflammation, myocardial apoptosis, angiogenesis and endothelial cell proliferation and migration, and showed that the NRG1-ErbB4 pathway might be an important component in both MOTS-c and exercise induced attenuation of cardiac dysfunction in diabetes. Moreover, our findings suggest that MOTS-c activates NRG1-ErbB4 signaling and mimics exercise-induced cardio-protection in diabetes.

Authors

Li, Shunchang; Wang, Manda; Ma, Jiacheng; Pang, Xiaoli; Yuan, Jinghan; Pan, Yanrong; Fu, Yu; Laher, Ismail

Keywords

MOTS-caerobic exercisemyocardiumtranscriptometype 2 diabetes (T2D)