The mitochondrial signaling peptide MOTS-c improves myocardial performance during exercise training in rats

Abstract

Cardiac remodeling is a physiological adaptation to aerobic exercise and which is characterized by increases in ventricular volume and the number of cardiomyocytes. The mitochondrial derived peptide MOTS-c functions as an important regulator in physical capacity and performance. Exercise elevates levels of endogenous MOTS-c in circulation and in myocardium, while MOTS-c can significantly enhance exercise capacity. However, the effects of aerobic exercise combined with MOTS-c on cardiac structure and function are unclear. We used pressure–volume conductance catheter technique to examine cardiac function in exercised rats with and without treatment with MOTS-c. Surprisingly, MOTS-c improved myocardial mechanical efficiency, enhanced cardiac systolic function, and had a tendency to improve the diastolic function. The findings suggest that using exercise supplements could be used to modulate the cardiovascular benefits of athletic training.

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

“…NRG1-ErbB4-C/EBPβ signaling is a key pathway implicated in regulating the adaptation in cardiomyocytes induced by exercise ( 46 , 47 ). Our previous findings suggested that both MOTS-c and aerobic exercise improved myocardial performance in rats ( 48 ). Based on the results of function enrichment analysis of DEGs and the exercise-like effects of MOTS-c in myocardium, we determined the mRNA and protein expression of NRG1 and ErbB4 to explore the molecular mechanisms of MOTS-c induced beneficial effects in cardiac.…”

MOTS ‐c increases in skeletal muscle following long‐term physical activity and improves acute exercise performance after a single dose

“…MOTS‐c is a mitochondrial‐encoded peptide that improves age‐related skeletal muscle insulin resistance and enhances adaptation to metabolic stress (Kim et al, 2018 , 2019 ; Reynolds et al, 2021 ). Its potential as an important regulator of systemic metabolism was highlighted in a series of studies examining changes in circulating MOTS‐c following high‐intensity exercise (Reynolds et al, 2021 ; von Walden et al, 2021 ) and by exogenously providing MOTS‐c in rodent models (Reynolds et al, 2021 ; Yuan et al, 2021 ). The goal of this study was to better understand the relationship between MOTS‐c and exercise.…”

“…Mitochondrial open reading frame (ORF) of the 12S rRNA type‐c (MOTS‐c) has emerged as a strong candidate for influencing intracellular communication and whole‐body physiology (Kim et al, 2017 ; Kim et al, 2018 ; Lee et al, 2016 ; Li & Laher, 2015 , Lu, Tang, et al, 2019 ; Reynolds et al, 2021 ; Yuan et al, 2021 ). MOTS‐c is abundantly expressed in skeletal muscle (D'Souza et al, 2020 ; Lee et al, 2015 ) and functions, in part, to increase glucose metabolism by enhancing insulin sensitivity, energy expenditure, and heat production (Lee et al, 2015 ).…”

Mitochondrial-Derived Peptides in Diabetes and Its Complications

“…Activating AMPK, increasing the phosphorylation level of eNOS, and decreasing the expression of the apoptotic factor Bax can help reduce the myocardial infarction area, enhance cardiac function, improve the survival rate of myocardial cells, and play a cardiac protective role in a dose-dependent manner (HNG,2 mg/kg is the best) in the MI-R mouse model. Yuan et al (61) investigated the effects of MOTS-c on cardiac function and structure of rats during chronic aerobic exercise by intraperitoneal injection of MOTS-C, and detected echocardiography by HEMO dynamics with HE staining. After analyzing cardiac function, it was found that MOTS-c could improve cardiac mechanical efficiency, enhance cardiac systolic function, and have a tendency to improve diastolic function, thus improving cardiac function.…”

“…Yuan et al. ( 61 ) investigated the effects of MOTS-c on cardiac function and structure of rats during chronic aerobic exercise by intraperitoneal injection of MOTS-C, and detected echocardiography by HEMO dynamics with HE staining. After analyzing cardiac function, it was found that MOTS-c could improve cardiac mechanical efficiency, enhance cardiac systolic function, and have a tendency to improve diastolic function, thus improving cardiac function.…”