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

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

doi:10.3389/fendo.2022.812032

Cited by 16 publications

(16 citation statements)

References 72 publications

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“…Li et al, MOTS-c therapy and regular aerobic exercise for 8 weeks altered 98 and 47 pathogenic genes, respectively, with 24 genes related to angiogenesis, inflammation, and apoptosis overlapping. These data imply that both MOTS-c and exercise reduce diabetic heart dysfunction through similar pathways [ 113 ].…”

Section: What Are Mitochondrial Derived Peptides (Mdps)?mentioning

confidence: 99%

MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases

Mohtashami

Singh

Salimiaghdam

et al. 2022

IJMS

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MOTS-c, a 16 amino acid mitochondrial derived peptide, is encoded from the 12S rRNA region of the mitochondrial genome. Under stress conditions, MOTS-c translocates to the nucleus where it regulates a wide range of genes in response to metabolic dysfunction. It is colocalized to mitochondria in various tissues and is found in plasma, but the levels decline with age. Since MOTS-c has important cellular functions as well as a possible hormonal role, it has been shown to have beneficial effects on age-related diseases including Diabetes, Cardiovascular diseases, Osteoporosis, postmenopausal obesity and Alzheimer. Aging is characterized by gradual loss of (mitochondrial) metabolic balance, decreased muscle homeostasis and eventual diminished physical capability, which potentially can be reversed with MOTS-c treatment. This review examines the latest findings on biological effects of MOTS-c as a nuclear regulatory peptide and focuses on the role of MOTS-c in aging and age-related disorders, including mechanisms of action and therapeutic potential.

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Section: What Are Mitochondrial Derived Peptides (Mdps)?mentioning

confidence: 99%

MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases

Mohtashami

Singh

Salimiaghdam

et al. 2022

IJMS

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show abstract

“…Furthermore, human studies showed that exercise increased MOTS-c levels in skeletal muscle and blood circulation, indicating that MOTS-c is a mitochondrial-derived peptide induced by skeletal muscle exercise ( 9 , 10 ). Additionally, more and more studies have revealed the importance of MOTS-c in regulating obesity and diabetes ( 11 , 12 ), longevity ( 13 ), and cardiovascular disease ( 14 ). Specifically, this paper discusses the application of mitochondrial-derived peptides, including MOTS-c, in the treatment of diseases and anticipates the future development direction of MOTS-c combining synthetic biology to provide new ideas on how it can be developed and applied.…”

Section: Introductionmentioning

confidence: 99%

MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation

2023

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Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c) is a mitochondrial-derived peptide composed of 16 amino acids encoded by the 12S rRNA region of the mitochondrial genome. The MOTS-c protein is transferred to the nucleus during metabolic stress and directs the expression of nuclear genes to promote cell balance. Different tissues co-expressed the protein with mitochondria, and plasma also contained the protein, but its level decreased with age. In addition, MOTS-c has been shown to improve glucose metabolism in skeletal muscle, which indicates its benefits for diseases such as diabetes, obesity, and aging. Nevertheless, MOTS-c has been used less frequently in disease treatment, and no effective method of applying MOTS-c in the clinic has been developed. Throughout this paper, we discussed the discovery and physiological function of mitochondrial-derived polypeptide MOTS-c, and the application of MOTS-c in the treatment of various diseases, such as aging, cardiovascular disease, insulin resistance, and inflammation. To provide additional ideas for future research and development, we tapped into the molecular mechanisms and therapeutic potentials of MOTS-c to improve diseases and combined the technology with synthetic biology in order to offer a new approach to its development and application.

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“…Rats in group C were placed on the non-moving treadmill (i. e., no exercise) for 60 minutes. Compressed air and tactile stimuli were used to prompt continuous running of rats during exercise 25 .…”

Section: Methodsmentioning

confidence: 99%

Time-dependent Effects of Moderate- and High-intensity Exercises on Myocardial Transcriptomics

Pang

et al. 2022

Int J Sports Med

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The heart is a highly adaptable organ that responds to changes in functional requirements due to exposure to internal and external stimuli. Physical exercise has unique stimulatory effects on the myocardium in both healthy individuals and those with health disorders, where the effects are primarily determined by the intensity and recovery time of exercise. We investigated the time-dependent effects of different exercise intensities on myocardial transcriptional expression in rats. Moderate intensity exercise induced more differentially expressed genes in the myocardium than high intensity exercise, while 16 differentially expressed genes were down-regulated by moderate intensity exercise but up-regulated by high intensity exercise at 12 h post- exercise. Both Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that moderate intensity exercise specifically regulated gene expression related to heart adaptation, energy metabolism, and oxidative stress, while high intensity exercise specifically regulated gene expression related to immunity, inflammation, and apoptosis. Moreover, there was increased expression of Tbx5, Casq1, Igsf1, and Ddah1 at all time points after moderate intensity exercise, while there was increased expression of Card9 at all time points after high intensity exercise. Our study provides a better understanding of the intensity dependent effects of physical exercise of the molecular mechanisms of cardiac adaptation to physical exercise.

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

Cited by 16 publications

References 72 publications

MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases

MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases

MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation

Time-dependent Effects of Moderate- and High-intensity Exercises on Myocardial Transcriptomics

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