MOTS-c Peptide Attenuated Diabetic Cardiomyopathy in STZ-Induced Type 1 Diabetic Mouse Model
Nan Wu1, Caijie Shen1, Jian Wang1
1Department of Cardiovascular Medicine, The First Affliated Hospital of Ningbo University, Ningbo, 315000, Zhejiang, China.
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.
Insights
Mitochondrial peptide MOTS-c shows promise in treating diabetic cardiomyopathy. This study found MOTS-c improved heart function and structure in diabetic mice by activating AMPK signaling and reducing inflammation.
Area of Science:
- Cardiovascular Research
- Metabolic Diseases
- Mitochondrial Biology
Background:
- Diabetic cardiomyopathy (DCM) is a significant complication of diabetes with limited treatment options.
- Mitochondrial-derived peptide MOTS-c has demonstrated therapeutic potential in various heart conditions.
- The efficacy of MOTS-c in DCM has not been previously established.
Purpose of the Study:
- To investigate the therapeutic effects of MOTS-c in a mouse model of type 1 diabetes-induced DCM.
- To determine if MOTS-c can ameliorate cardiac dysfunction and remodeling in diabetic hearts.
- To explore the molecular mechanisms underlying MOTS-c's action in DCM.
Main Methods:
- Type 1 diabetes was induced in mice using streptozotocin (STZ).
- Diabetic mice were treated with or without MOTS-c via subcutaneous osmotic pump for 12 weeks.
- Cardiac function, histology, and molecular markers were assessed post-treatment.
Main Results:
- Diabetic mice displayed significant cardiac dysfunction, dilatation, and adverse remodeling.
- MOTS-c treatment substantially improved cardiac function and structure in diabetic mice.
- MOTS-c reversed AMPK signaling deactivation and reduced cardiac inflammation.
Conclusions:
- MOTS-c exhibits a protective effect against diabetic cardiomyopathy.
- The protective mechanism involves activation of the AMPK pathway and inhibition of inflammation.
- MOTS-c demonstrates therapeutic potential for DCM, warranting further clinical investigation.
