MOTS-c Peptide Attenuated Diabetic Cardiomyopathy in STZ-Induced Type 1 Diabetic Mouse Model.

Cardiovascular drugs and therapy2025PMID: 38141139

View on PubMed DOI: 10.1007/s10557-023-07540-2

Animal StudyMOTS-C

Plain Language Summary

STZ-induced T1DM mouse study demonstrating that MOTS-c treatment attenuates diabetic cardiomyopathy by improving cardiac structure, reducing fibrosis, and restoring mitochondrial function and energy metabolism in the type 1 diabetic heart. Extends MOTS-c's cardiotherapeutic evidence to the T1DM context. Provides the first evidence for MOTS-c efficacy in T1DM-associated cardiomyopathy—an increasingly recognized cardiac complication in T1DM where mitochondrial dysfunction drives structural and functional deterioration, establishing MOTS-c as a potential cardioprotective strategy in insulin-dependent diabetes.

Abstract

BACKGROUND: Diabetic cardiomyopathy (DCM) pathogenesis is a common complication of diabetes, but effective treatments remain limited. Mitochondrial-derived peptide MOTS-c has shown therapeutic promise in animal models of various heart diseases, but its efficacy in DCM is unknown. This study investigates the effects of MOTS-c treatment in a mouse model of type 1 diabetes-induced DCM. METHODS: Type 1 diabetes (T1DM) was induced in mice by streptozotocin (STZ) injection. After diabetes establishment, the mice were randomly dividend into two groups treated with or without MOTS-c peptide, which was administered subcutaneously by osmotic pump for 12 weeks. At the end of the experiment, cardiac function, histology, and molecular changes were determined. RESULTS: The results showed that diabetic mice exhibited significant cardiac dysfunction, dilatation, and adverse cardiac remodeling. MOTS-c treatment markedly ameliorated these diabetes-associated myocardial function and structure abnormalities. Additionally, MOTS-c reversed AMPK signaling deactivation and inhibited inflammation in the diabetic heart. CONCLUSIONS: Our data demonstrated a protective effect of MOTS-c against diabetic cardiomyopathy potentially by activating the AMPK pathway and inhibiting inflammation. These findings demonstrate the therapeutic efficacy of MOTS-c for diabetic cardiomyopathy and warrant further investigation into its clinical potential.

Authors

Wu, Nan; Shen, Caijie; Wang, Jian; Chen, Xiaomin; Zhong, Peng

Keywords

AMPKCardiac remodelingDiabetic cardiomyopathyInflammationMOTS-c