While many peptides currently available for research exhibit the potential to stimulate growth hormone secretion from the anterior pituitary gland, studies suggest Mots-c may exhibit a distinct mechanism of action. Today, our focus lies in discussing this particular peptide.


Mots-c refers to mitochondrial-derived peptides, small bioactive molecules derived from the mitochondria, the energy-producing organelle.


In recent years, considerable research has been conducted on the potential of various peptides derived from mitochondria. Researchers speculate that Mots-c is a peptide composed of 16 amino acids transcribed specifically from the mitochondrial genome [i].


Comprehensive investigations and meticulous analysis suggest that Mots-c may be pivotal in regulating multiple metabolic pathways in energy production. Scientists hypothesise the peptide may regulate physical activity and glucose metabolism [ii].


Mots-c Peptide: Mechanism of Action


In contrast to numerous other peptides, studies suggest Mots-c may not exert its effects through stimulating growth hormone secretion. Instead, it functions by augmenting glucose metabolism through multiple pathways. More energy can be expended with enhanced glucose metabolism, facilitating the efficient operation of various physiological processes.


Metabolic dysfunction, characterised by excessive caloric consumption without corresponding physical exertion, has been identified as a potential precursor to diabetes, obesity, and metabolic syndrome [iii]. Reports indicate that overabundance of food can lead to mitochondrial dysfunction through specific mechanisms.


This is where the concept of Mots-c becomes relevant. Before proceeding, it is important to understand functional metabolism. Metabolism encompasses the efficient acquisition and utilisation of glucose stores and the optimal functioning of insulin and mitochondria.


Research suggests one of the primary functions of Mots-c may be to enhance insulin sensitivity, particularly in the skeletal muscles. Researchers speculate this may be achieved by auguring the AMP-activated protein kinase (AMPK) pathway [iv]. This process may facilitate the utilisation of additional storage biomolecules, thereby augmenting energy expenditure to operate various metabolic pathways.


Scientific research suggests it has been reported that Mots-c may have the potential to enhance glucose clearance rather than reduce hepatic glucose production. It has been speculated believed to decrease non-fasting glucose levels and enhance glucose tolerance tests. In addition, Mots-c has been scientifically suggested to enhance the process of bone cell differentiation and provide relief from symptoms associated with osteoporosis. Nevertheless, the precise mechanism remains under investigation.


Mots-c Peptide and Weight


Studies on MOTS-c have been frequently employed in the context of weight reduction. Researchers speculate that Mots-c may enhance the utilisation of energy stores, such as glucose and fatty acids. This may decrease fatty tissue for energy generation and consumption [v].


A notable reduction in obesity was observed in rats that were presented with a high-fat diet and supplemented with Mots-c, as speculated by the researchers.


Mots-c Peptide and Physical Activity 


Scientists hypothesise that given its alleged capacity to improve insulin sensitivity and augment energy generation, Mots-c may be utilised to optimise peak physical activity. The peptide may have the potential to enhance endurance and augment energy levels during cardiovascular exertion, research suggests.


Mots-c Peptide and Mitochondria


Research trials have also suggested a potentially protective effect of Mots-c on mitochondrial health. The peptide may protect mitochondrial DNA by mitigating the damaging impact of free radicals and oxidative stressors.


Mots-c Peptide and Cardiovascular Performance


In addition, there is prevailing speculation that decreased levels of MOTS-c may contribute to the development of endothelial dysfunction. Consequently, rats that received MOTS-c peptide appeared to exhibit endothelial and epicardial blood vasculature enhancements, resulting in improved cardiac functions [vi].


Mots-c Peptide and Ageing


Finally, studies suggest the cellular differentiation capacity of this entity may contribute to the mitigation of heightened inflammation and the development of osteoporosis in skeletal structures. This method may represent a potential approach for decelerating ageing [vii].


MOTS-c, IGF1-LR3, and PEG MGF Peptide Blend


Research has expanded beyond the close examination of Mots-c, with IGF1-LR3 and PEG-MGF all synergistically and separately investigated for supposed similar properties. Studies suggest IGF1-LR3 may stimulate fatty acid oxidation and augment muscle regeneration by inhibiting myostatin. Furthermore, it may enhance the effects by incorporating PEG-MGF as an additional component.


If you are a researcher interested in purchasing Mots-c peptide for your research studies, click here. Be mindful that these compounds are meant to be used by licensed professionals only.


This article is part of the HealthManagement.org Point-of-View Programme.


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[i] Zheng Y, Wei Z, Wang T. MOTS-c (2023) A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 14:1120533.

[ii] Lee C, Kim KH, Cohen P (2016) MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med. 100:182-187.

[iii] Lee C, Zeng J, Drew BG et al. (2015) The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 21(3):443-454.

[iv] Mohtashami Z, Singh MK, Salimiaghdam N et al. (2022) MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. Int J Mol Sci. 23(19):11991.

[v] Reynolds JC, Lai RW, Woodhead JST et al. (2021) MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 12(1):470.

[vi] Yuan J, Wang M, Pan Y et al. (2021) The mitochondrial signaling peptide MOTS-c improves myocardial performance during exercise training in rats. Sci Rep. 11(1):20077.

[vii] Kong BS, Lee C, Cho YM (2023) Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases [published online ahead of print, 2023 Feb 24]. Diabetes Metab J. 10.4093/dmj.2022.0333.

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peptide, Mots-c, mitochondria, metabolic dysfunction, metabolic pathways, functional metabolism MOTS-c Peptide and Mitochondrial Research