Properties and Research in MOTS-c

The mitochondrial oligopeptide MOTS-c has attracted much scientific attention because of its alleged potential for improving metabolic function. The list of possible properties of MOTS-c is believed to be long and may include:

• Possible impacts on weight
• Possible anti-ageing properties in cells
• Possible impact on cardiac function
• Possible brain defence
• Possible improvement of muscle cell development
• Possible enhancement of cell reaction to stress

This paper discusses MOTS-c’s properties and potential to give researchers interested in studying it a head start. Additionally, we have included our recommended choice for an online supplier of research-grade MOTS-c.

MOTS-c Peptide: What is it?

MOTS-c was first proposed to study mitochondrial DNA and its potential for metabolic impact. Potentially involved in metabolic regulation and age-related physiological function, MOTS-c has yielded interesting study results since its 2015 discovery. Scientists suggest that MOTS-c may affect insulin sensitivity, cellular stress response, and energy metabolism.

Metabolic illnesses, such as type 2 diabetes and obesity, are now the centre of attention in MOTS-c research. A potential path for the study is its alleged function in increasing physical activity and its anti-ageing impact on cells, which researchers are currently investigating.

Phase 1a clinical studies for CB4211, an analogue of MOTS-c, were finished in 2021. It is now being tested in non-alcoholic fatty liver disease (NFLD).

MOTS-c Peptide: Mechanism of Action

The Metabolic Open Reading Frame of the 12S rRNA Type-c, or MOTS-c, is a peptide from the mitochondrial genome. It consists of 16 amino acids, and its structure may be believed to be comparable to that of other peptides regulating metabolism, such as SHLP2 and humanin. Here is the exact sequence of its amino acids: MRWQEMGYIFYPRKLR.

Yet, the exact process by which MOTS-c operates remains a mystery. On the other hand, it’s thought to work by stimulating the AMP-activated protein kinase (AMPK) pathway, a crucial player in glucose and lipid metabolism and a regulator of cellular energy balance.

Research indicates that MOTS-c may translocate to the nucleus during stress, regulating a wide range of genes related to metabolic failure. Because of its nuclear location, its possible role in regulating gene expression in metabolically demanding situations is highlighted. Investigations purport that MOTS-c may improve glucose uptake, mitochondrial activity, and insulin sensitivity by activating AMPK, which is believed to have several potential impacts. The results of these studies point to the possibility of examining MOTS-c in the context of metabolic diseases research, such as obesity and type 2 diabetes.

Regarding its pharmacokinetics, MOTS-c has been hypothesized to spread in circulation and is believed to be rather stable. Its levels decrease over time, while it is present in plasma and mitochondria in many organs. Findings imply that MOTS-c may not only have metabolic effects but may potentially also possess neuroprotective qualities. It has been theorised to enhance neuronal survival by shielding them from oxidative stress.

In addition, it has suggested encouraging outcomes in animal studies for the prevention of age-related illnesses such as Alzheimer’s, osteoporosis, postmenopausal problems, and muscle atrophy.

MOTS-c Peptide Potential

In preclinical research, MOTS-c has several suggested properties. Here are some possible properties connected with MOTS-c; however, more study is required to comprehend its research uses properly.

MOTS-c Peptide and Metabolism

Lee et al. (2015) performed mouse tests to learn how MOTS-c may affect weight control. For eight weeks, the scientists fed one group of mice a high-fat diet and MOTS-c. A separate set of mice received MOTS-c while fed a standard diet.

The research’s findings implied that no discernible weight loss occurred in the MOTS-c animals that were otherwise given an ordinary diet. On the other hand, mice who were given MOTS-c in addition to a high-fat diet appeared to exhibit a considerable decrease in overall weight.

Based on the results of this research, MOTS-c is speculated to have some impact in obesity-related cases in murine models. However, we must still learn how MOTS-c may affect weight loss when combined with a high-fat diet in these organisms.

Lu et al. (2019) discovered that metabolic abnormalities, including decreased energy expenditure, weight gain, and increased risks of cardiovascular and cancer-related illnesses, may be more common in the postmenopausal state. The research indicated that mice treated with MOTS-c might avoid the obesity and insulin resistance resulting from ovariectomy. In addition, MOTS-c was speculated to activate brown fat, decrease inflammation in white adipose tissue, and minimise fat storage. As a result, blood and liver fatty acid levels may drop.

Studies suggest that MOTS-c may be a potential research target for metabolic diseases such as type 2 diabetes and obesity due to its potential to enhance insulin sensitivity, control energy metabolism, and increase glucose absorption in peripheral tissues.

MOTS-c Peptide and Cell Aging

Numerous implications for cell health have been speculated about MOTS-c, a naturally-occurring peptide whose endogenous levels decline over time. Researchers gave MOTS-c peptide to research models for two weeks and suggested that mice of varying ages (2, 12, 22, and 23.5 months) appeared to have improved physical performance. As a result of this approach, scientists speculated on an improvement in their physical capacities and a postponement of age-related impairments.

As a result of dermal collagen loss, the dermo-epidermal interface flattens, and the extracellular matrix becomes disordered, contributing to the aging of skin cells. After presenting six-week-old mice with MOTS-c peptide, Li et al. (2019) suggested that skin collagen levels appeared elevated. One reason for this upsurge was believed to be that MOTS-c may have lowered IL-6 levels. This important inflammatory cytokine destroys collagen in dermal matrix metalloproteinase 1 (MMP1). It is believed that MOTS-c may delay skin cell ageing and increase dermal collagen formation by decreasing inflammation.

Researchers interested in further studying the potential of MOTS-c peptide or many other high-quality research compounds are encouraged to visit the www.corepeptides.com website. Please be aware that none of the substances mentioned in this article have received approval for human consumption, and only licensed individuals should purchase and use them for research.

References

[i] Fuku N, Pareja-Galeano H, Zempo H, Alis R, Arai Y, Lucia A, Hirose N The mitochondrial-derived peptide MOTS-c: a player in exceptional longevity?.Aging Cell. 2015 Dec;14(6):921-3

[ii] Mohtashami Z, Singh MK, Salimiaghdam N, Ozgul M, Kenney MC. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. Int J Mol Sci 2022 Oct 9;23(19):11991.

[iii] Gao Y, Wei X, Wei P, Lu H, Zhong L, Tan J, Liu H, Liu Z. MOTS-c Functionally Prevents Metabolic Disorders. Metabolites. 2023 Jan 13;13(1):125. doi 10.3390/metabo13010125.

[iv] Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021 Jan 20;12(1):470. doi 10.1038/s41467-020-20790-0.

[v] A Phase 1A/1B of study of CB4211in healthy non[1]obese subjects and subjects with non-alcoholic fatty liver disease – full-text view. Full-text view ClinicalTrials.gov (n.d.) Retrieved March 18, 2024, from https://clinicaltrials.gov/ct2/show/NCT03998514

[vi] Yang B, Yu Q, Chang B, Guo Q, Xu S, Yi X, Cao S. MOTS-c interacts synergistically with exercise intervention to regulate PGC-1α expression, attenuate insulin resistance and enhance glucose metabolism in mice via AMPK signaling pathway. Biochim Biophys Acta Mol Basis Dis. 2021 Jun 1;1867(6):166126. doi: 10.1016/j.bbadis.2021.166126. Epub 2021 Mar 13.

[vii] 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.