Studies suggest that peptides are amino acid chains that may serve important roles in various biological activities. Recently, mitochondrial ORF of the 12S rRNA type-c (MOTS-c) peptide has emerged as a promising compound in mitochondrial research.

The mitochondrial genome encodes a peptide that controls nuclear gene expression in the mitochondria in reaction to conditions like metabolic stress. It has suggested promise in anti-aging, anti-inflammatory, and metabolic studies in the laboratory. However, further study is required to understand the potential of MOTS-c fully.

The potential properties of MOTS-c peptide for sale, including improved muscular function, reduced insulin resistance, reduced inflammation, improved bone health, and improved metabolic and cardiovascular health, will be discussed.

Overview of the MOTS-c Peptide

The MOTS-c peptide is naturally produced. It is found in the energy-generating organelles of cells called mitochondria. The peptide has the amino acid sequence H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg-OH, and it is 16 amino acids in length.

Early studies examined its possible relevance in the context of research in age-related conditions such as diabetes, cardiovascular disease, osteoporosis, postmenopausal obesity, and Alzheimer’s disease. Studies suggest that “under stress circumstances, MOTS-c translocates to the nucleus where it controls a wide range of genes in response to metabolic dysfunction.” 

MOTS-c Peptide and Insulin Resistance

The prospect of MOTS-c in insulin resistance and metabolic studies are among its most actively studied potential properties. In metabolic diseases like insulin resistance, improving glucose metabolism in skeletal muscles has been suggested by many animal studies. Skeletal muscle glucose uptake may be increased, and visceral fat levels may be reduced as a result of this method of action, research suggests.

Activation of the AMPK pathway has been speculated to occur due to MOTS-c’s selective targeting of skeletal muscle and its inhibition of the folate cycle and its attached de novo purine production. Thus, it seemed that MOTS-c in mice may have prevented insulin resistance and diet-induced obesity caused by both aging and a high-fat diet.

In addition to its potential properties for cardiovascular health, MOTS-c has been suggested to increase thermogenesis in adipose tissue and promote the “browning” of white (beige) fat. The ERK signaling pathway is thought to be the mediator of MOTS-c’s actions.

Studies in gestational diabetes, a kind of diabetes caused by increased insulin resistance during pregnancy, have also purported that MOTS-c may be relevant. Findings suggest that hyperglycemia appeared dramatically decreased, insulin sensitivity and glucose tolerance seemed enhanced, and birth weight and the risk of neonatal mortality were reduced in a mouse subject of type 2 diabetes when MOTS-c was given daily during pregnancy.

MOTS-c seems to have an impact on skeletal muscles beyond only enhancing glucose absorption. The peptide may also affect muscle atrophy associated with obesity and type 2 diabetes, as suggested by findings from animal studies. In mice, MOTS-c seems to work by lowering plasma myostatin levels and increasing AKT phosphorylation, both of which suppress the activity of the muscle-wasting gene transcription factor FOXO1. Research suggests that dystrophic muscle atrophy may also be mitigated, especially in models of Duchenne muscular dystrophy (DMD).

MOTS-c Peptide and Cardiovascular Function

It has been hypothesized that MOTS-c peptides may have a protective impact on the heart muscle owing to increased mitochondria activity in the myocytes. One research study suggested that the peptide may have improved cardiac function and reduced inflammation in a mouse model of heart failure. The peptide seemed to increase antioxidant capacity in the hearts of mice, decrease cell apoptosis, and activate the AMPK pathway.

Studies in diabetic rats suggested that presentation of the peptide appeared to have enhanced myocardial mitochondrial impairment, maintained cardiac systolic and diastolic function, and modified 47 disease-causing genes related to apoptosis, immunoregulation, angiogenesis, and fatty acid metabolism, suggesting that MOTS-c may also help reduce the detrimental impact of type 2 diabetes on the heart.

Thanks to activating the AMPK and the anti-oxidative activities of the peptide, animal studies also suggest it may support the decrease of inflammation in the heart and shield against vascular calcification (VC), which is a consequence of atherosclerosis.

Heart systolic function, mechanical heart efficiency, and diastolic function are all hypothesized to be enhanced by MOTS-c in mice. These findings purport that MOTS-c may enhance the cardiovascular advantages of exercise. Researchers have speculated that stimulating the NRG1-ErbB4-C/EBP pathway may have comparable effects on cardiac function as exercise.

MOTS-c Peptide and Bone

Investigations purport that MOTS-c may improve bone health via its proposed potential to activate phosphorylated AMPK. One research suggests that in a mouse model of osteoporosis, MOTS-c peptide appears to dramatically block osteoclast development and minimize bone loss, as measured by micro-CT examination. As a result of their research, the team speculated that “MOTS-c may wield as a blocker of osteoporosis condition via AMPK dependent inhibition of osteoclastogenesis.”

In another study, researchers hypothesized that ultra-high molecular weight polyethylene particle-induced osteolysis in an animal model appeared to have resulted in less bone loss and inflammation. Osteoclastogenesis seemed to be suppressed by MOTS-c because it may have increased the osteoprotegerin to receptor activator of nuclear factor kappa B ligand ratio in osteocytes.

References

[i] Ming W, Lu G, Xin S, Huanyu L, Yinghao J, Xiaoying L, Chengming X, Banjun R, Li W, Zifan L. Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation. Biochem Biophys Res Commun. 2016 Aug 5;476(4):412-419. doi: 10.1016/j.bbrc.2016.05.135. Epub 2016 May 26. PMID: 27237975.

[ii] Lee C, Kim KH, Cohen P. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med. 2016 Nov;100:182-187. doi: 10.1016/j.freeradbiomed.2016.05.015. Epub 2016 May 20. PMID: 27216708; PMCID: PMC5116416.

[iii] Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015 Mar 3;21(3):443-54. doi: 10.1016/j.cmet.2015.02.009. PMID: 25738459; PMCID: PMC4350682.

[iv] Lu H, Tang S, Xue C, Liu Y, Wang J, Zhang W, Luo W, Chen J. Mitochondrial-Derived Peptide MOTS-c Increases Adipose Thermogenic Activation to Promote Cold Adaptation. Int J Mol Sci. 2019 May 17;20(10):2456. doi: 10.3390/ijms20102456. PMID: 31109005; PMCID: PMC6567243.

[v] Yin Y, Pan Y, He J, Zhong H, Wu Y, Ji C, Liu L, Cui X. The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus. Pharmacol Res. 2022 Jan;175:105987. doi: 10.1016/j.phrs.2021.105987. Epub 2021 Nov 17. PMID: 34798268.