Research
MOTS-c Peptide Research
MOTS–c is a 16-amino-acid peptide encoded in the mitochondrial genome. MOTS–c targets muscle and regulates metabolism via the folate-purine-AMPK pathway. MOTS–c mediates mitochondrial regulation of insulin and metabolic homeostasis.
MOTS-c Structure
PubChem CID: 146675088
Molecular Formula: C101H152N28O22S2
Molecular Weight: 2174.6
CAS Number: 1627580-64-6
Sequence: MRWQEMGYIFYPRKLR
Synonyms: UNII-A5CV6JFB78, 1627580-64-6, A5CV6JFB78, Mitochondria-derived peptide mots-c
MOTS-c and Metabolism
MOTS-c plays a vital role in regulating metabolic functions throughout the body, particularly in glucose utilization for energy production. Its impact on skeletal muscle and glucose metabolism has far-reaching implications for obesity, diabetes, exercise, and longevity. Notably, MOTS-c exhibits close associations with amino acid, carbohydrate, and lipid metabolism.
Key findings reveal that MOTS-c promotes metabolic homeostasis, reducing obesity and insulin resistance. It enhances cellular glucose flux, leading to reduced glucose levels in mice on a normal diet.
Furthermore, MOTS-c improves systemic insulin sensitivity, as evidenced by enhanced glucose clearance in glucose tolerance tests and hyperinsulin-orthoglycemic clamping studies. In post-menopausal mice, MOTS-c administration activates brown fat, lowers inflammatory markers in white adipose tissue, decreases fatty acid levels in serum and liver, and limits weight gain. AMPK activation by MOTS-c minimizes fat deposition, restores energy balance, and improves insulin sensitivity.
Additionally, MOTS-c prevents fat accumulation in mice by modulating sphingolipid metabolism pathways. Overall, MOTS-c exerts regulatory effects on metabolic flexibility, homeostasis, mitochondrial energy regulation, and protection against age and diet-related metabolic disorders.
References:
https://pubmed.ncbi.nlm.nih.gov/27216708/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570330/
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03885-2
https://www.mdpi.com/2218-1989/13/1/125
MOTS-c and Insulin Sensitivity
MOTS-c has been extensively studied and demonstrated to augment insulin sensitivity through the inhibition of the folate cycle and its tethered de novo purine biosynthesis, consequently instigating AMPK activation.
Additionally, MOTS-c exhibits a protective effect against obesity and fatty liver by increasing beta-oxidation and glucose uptake.
Notably, this peptide is activated in response to stress and exercise, while its expression diminishes with advancing age. These findings suggest that MOTS-c holds significant potential in promoting healthy aging and averting metabolic diseases.
References:
https://pubmed.ncbi.nlm.nih.gov/25738459/
https://pubmed.ncbi.nlm.nih.gov/31293078/
https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-03885-2
https://link.springer.com/article/10.1007/s00109-019-01758-0
MOTS-c and Osteoporosis
Studies indicate that MOTS-c could potentially exert a positive influence on osteoporosis by stimulating the synthesis of type I collagen in osteoblasts via the TGF-β/SMAD signaling pathway. Type I collagen serves as a crucial constituent of the bone matrix, contributing to bone strength and overall quality.
Furthermore, MOTS-c may enhance bone cell differentiation and alleviate symptoms associated with osteoporosis by modulating genes involved in stress adaptation and metabolism. As a result, MOTS-c shows promise in the prevention and treatment of osteoporosis through its capacity to enhance bone formation and mitigate bone loss.
References:
https://pubmed.ncbi.nlm.nih.gov/31081069/
https://www.researchgate.net/publication/329516017_MOTS-c_improves_osteoporosis_by_promoting_osteogenic_differentiation_of_bone_marrow_mesenchymal_stem_cells_via_TGF-gSmad_pathway
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570330/