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Key Benefits
Biologic Description
MOTS-c, a mitochondrial-derived peptide encoded by the 12S rRNA region of the mitochondrial genome, has attracted considerable attention since its discovery in 2015 for its potential role in metabolic regulation and age-related conditions. Unlike typical peptides, MOTS-c is translated from rRNA, which primarily aids ribosomal function, making its genetic translation process unique.
This compound is known for its diverse effects on cellular metabolism, insulin sensitivity, mitochondrial function, and aging processes. Its abilities include improving glucose uptake, enhancing insulin sensitivity, promoting the formation of new mitochondria, and reducing oxidative stress, all contributing to improved metabolic health and cellular function. These properties suggest potential for managing conditions like diabetes, obesity, and age-related diseases.
The mechanism of MOTS-c involves translocation to the nucleus in response to metabolic stress, where it modulates adaptive gene expression. Known as a "mitokine," it circulates in the bloodstream, playing a crucial role in metabolic functions. The peptide's levels are influenced by age and the folate cycle, with a notable decline in older individuals. Under stress conditions, MOTS-c moves from the mitochondria to the nucleus, impacting levels of key enzymes such as AMPK and AICAR, essential in regulating energy balance.
MOTS-c's potential in treating metabolic disorders has been highlighted in various studies. For instance, in postmenopausal women, it has shown promise in preventing obesity and insulin resistance. This was demonstrated in a study with ovariectomized mice, where MOTS-c treatment led to activation of brown fat and reduced inflammation, thus preventing the development of obesity and insulin resistance.
In the context of obesity management, research has indicated that MOTS-c can play a significant role, particularly when combined with high-fat diets in mouse models. However, the exact mechanisms and implications for humans remain to be fully understood.
The peptide's role in anti-aging is also notable, with studies showing its impact on physical performance and mitigation of age-related decline, suggesting its potential as a therapeutic target for healthy aging. In cardiovascular health, MOTS-c has demonstrated efficacy in preventing vascular calcification by activating AMPK signaling pathways.
Additionally, MOTS-c's benefits extend to muscle performance, particularly when used alongside exercise. It has been found to activate skeletal muscle AMPK and influence genes related to angiogenesis, inflammation, and apoptosis, enhancing mitochondrial function and energy metabolism.
Despite these promising findings, MOTS-c's therapeutic applications require further exploration through ongoing research to fully understand its therapeutic potential and implications in various physiological and pathological conditions. Researchers are encouraged to keep up with emerging findings in this rapidly evolving field.
Dosage Guidelines
Researchers exploring the effects of MOTS-c on obesity can refer to the following sample dosing protocol. It is recommended to administer 5mg of MOTS-c through a subcutaneous injection in the morning, with the frequency set at every five days. This regimen should be maintained for a duration of 20 days. After completing the first course, it is suggested to repeat the cycle six months later.
In addition to this protocol, it's important to incorporate lifestyle modifications for effective weight management. These include maintaining a healthy diet, engaging in regular exercise, and ensuring proper sleep.
For the supply, researchers will need two 10mg vials of MOTS-c to complete one course as per this protocol. It's crucial to perform injections with strict adherence to aseptic handling protocols. In case of severe adverse reactions, the therapy should be discontinued.
The storage of MOTS-c vials is another important aspect. They should be kept in a cool, dark area and used before the expiration date. To ensure the highest quality and purity of the peptide, it is advisable to source all research peptides from suppliers that adhere to leading quality assurance standards. This ensures the reliability and consistency of the research outcomes.
5 mg
Every 5 Days
For 20 Days
Side Effects
To date, studies involving MOTS-c have not reported significant adverse side effects. Laboratory animal research and in vitro experiments have shown the beneficial effects of MOTS-c on various health parameters, demonstrating its efficacy without apparent toxicity. However, it is crucial to conduct further research to fully assess the long-term safety and potential side effects of MOTS-c in human subjects.
CohBar, a biotech company, carried out a clinical study on CB4211, a MOTS-c analog, targeting individuals with nonalcoholic steatohepatitis (NASH) and obesity. The findings from this study indicated that CB4211 was well-tolerated and appeared safe, with no major adverse effects reported. These results offer valuable insights into the safety profile of MOTS-c analogs and their possible therapeutic uses.
As an injectable peptide, certain adverse effects are associated with MOTS-c, including irritation, swelling, or redness at the injection site, formation of nodules or lumps, pain or discomfort during or after injection, bruising, discoloration, and rare allergic reactions like hives or breathing difficulties. To mitigate these risks, researchers are encouraged to source MOTS-c from reputable suppliers and adhere to aseptic handling practices in laboratory settings.
The safety of MOTS-c, a relatively new compound, is still being evaluated. Although no significant side effects have been reported, researchers must familiarize themselves with all relevant clinical data regarding the potential risks associated with experimental administration of MOTS-c. Handling of this peptide should be confined to qualified researchers and laboratory professionals, and self-administration outside of scientific research contexts is strictly inadvisable.
References:
MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism
Mitochondria are ancient organelles that are thought to have emerged from once free-living α-proto-bacteria. As such, they still possess several bacterial-like qualities, including a semi-autonomous genetic system, complete with an independent genome and a unique genetic code. The bacterial-like circular mitochondrial DNA (mtDNA) has been described to encode 37 genes, including 22 tRNAs, 2 rRNAs, and 13 mRNAs. Two additional peptides reported to originate from the mtDNA, namely humanin (Hashimoto et al., 2001; Ikone et al., 2003; Guo et al., 2003) [1–3] and MOTS-c (mitochondrial ORF of the twelve S c) (Lee et al., 2015) [4], indicate a larger mitochondrial genetic repertoire (Shokolenko and Alexeyev, 2015) [5]. These mitochondrial-derived peptides (MDPs) have profound and distinct biological activities and provide a paradigm-shifting concept of active mitochondrial-encoded signals that act at the cellular and organismal level (i.e. mitochondrial hormone) (da Cunha et al., 2015; Quiros et al., 2016) [6,7]. Considering that mitochondria are the single most important metabolic organelle, it is not surprising that these MDPs have metabolic actions. MOTS-c has been shown to target the skeletal muscle and enhance glucose metabolism. As such, MOTS-c has implications in the regulation of obesity, diabetes, exercise, and longevity, representing an entirely novel mitochondrial signaling mechanism to regulate metabolism within and between cells.
Author: Changhan Lee, Kyung Hwa Kim, and Pinchas Cohen
Publication Date: 2016 Dec
MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction
The postmenopausal state is associated with an increased risk of metabolic disorder including reduced energy expenditure and weight gain, leading to higher cardiovascular and cancer risks among other diseases. Mitochondrial-derived peptide (MOTS-c) is a 16-amino acid peptide encoded by mitochondrial DNA. Here, we showed that MOTS-c treatment in mice prevented ovariectomy-induced obesity and insulin resistance. After ovariectomy, low levels of estrogens increased fat mass overload and disturbed normal adipose function, forcing the development of insulin resistance. MOTS-c treatment increased brown fat activation and reduced OVX-induced fat accumulation and inflammatory invasion in white adipose tissue, which contributes to the lower level of fatty acid in serum and liver. Moreover, MOTS-c activated AMPK pathway to improve energy dissipation and insulin sensitivity. And a blocker of AMPK pathway was found to attenuate the role of MOTS-c in the regulation of adipocyte lipid metabolism. In conclusion, MOTS-c is a high potential candidate for chronic treatment of menopausal induced metabolic dysfunction. KEY MESSAGES: • MOTS-c prevents ovariectomy (OVX)-induced body weight gain and insulin resistance. • MOTS-c reduces fat mass and suppresses inflammatory response under OVX condition. • MOTS-c sustains the activity of the brown adipose under OVX condition. • MOTS-c mediates AMPK pathway activation to control adipose metabolic homeostasis.
Authors: Huanyu Lu, Ming Wei, Yue Zhai, Qingyang Li, Zichen Ye, Li Wang, Wenjing Luo, Jingyuan Chen, Zifan Lu
Published: 2019 Feb
MOTS-c can regulate the synthesis of type I collagen in osteoblasts by regulating TGF-β/ SMAD pathway, thereby improving osteoporosis
Cell viability was significantly increased after treatment of 1.0 μM MOTS-c for 24 h or 0.5 μM MOTS-c for 48 h in a time-dependent manner. The mRNA and protein expressions of TGF-β, SMAD7, COL1A1 and COL1A2 in hFOB1.19 cells were dependent on the concentration of MOTS-c. In addition, MOTS-c increased the expressions of COL1A1 and COL1A2, which were partially reversed by knockdown of TGF-β or SMAD7.
Authors: N Che, W Qiu, J-K Wang, X-X Sun, L-X Xu, R Liu, L Gu
Published: 2019 Apr
The role of mitochondria-derived peptides in cardiovascular disease: Recent updates
Mitochondria-derived peptides (MDPs) are a series of peptides encoded by mitochondrial DNA, and have similar functions to mitochondria. At present there are three types of MDPs that have been found, including Humanin, MOTS-c and SHLP1-6. They are new metabolic regulators of human body, and play a cytoprotective role in maintaining mitochondrial function and cell viability under pressure. Increasingly researchers have demonstrated that MDPs have proved effects on cell survival, metabolism, response to stressors, and inflammation in vivo and vitro. Recently with the advance of research, it have shown that MDPs have significant effects on the development of cardiovascular diseases (CVD). In this review, we will cover the relationships of MDPs with cardiovascular risk factors, myocardial ischemia, reperfusion injury, myocardial fibrosis, and coronary microcirculatory dysfunction, and also their possible pathogenic mechanisms. MDPs are considered to be novel biomarkers or therapeutic targets for CVD.
Authors: Yingxi Yang, Huijuan Gao, Huan Zhou, Qi Liu, Zhongwen Qi, Ying Zhang, Junping Zhang
Published: 2019 Sep