Mitochondrial ORF of the twelve S c (MOTS-c)

Potential Benefits of Mitochondrial ORF of the twelve S c (MOTS-c)

• Treats obesity [1-12]
• Improves blood sugar levels and treats symptoms of diabetes [13-18]
• Improves heart health [19-24]
• Fights bone loss [25-27]
• Increases life expectancy [28-34]
• Improves exercise tolerance [35-51]
• Fights bacterial infection [52]

What is MOTS-c?

The mitochondria are considered the “powerhouses of cells”. They are organelles that work like the digestive system which ingests nutrients, breaks them down, and produces fuel or energy for the cells’ biological functions. The mitochondria also pass down information via several signaling molecules in order to enhance communication between each cell. Mitochondrial ORF of the twelve S c (MOTS-c) is one of the mitochondrial-derived peptides (MDPs) that plays an integral role in a wide array of metabolic functions such as glucose metabolism, muscle synthesis, and maintenance of metabolic homeostasis (balance).

How MOTS-c Works?

MOTS-c holds much potential as a therapeutic option for a multitude of medical conditions because of its unique ability to positively affect various bodily functions. It improves muscle metabolism and function via AMPK activation. Following metabolic stress, MOTS-c regulates certain genes involved in blood sugar restriction and antioxidant responses. In addition, it also plays a role in the synthesis of type I collagen by osteoblasts (bone-forming cells).

Chemical Structure of MOTS-c

Research on MOTS-c

Treats Obesity

Obesity is one of the world’s major health concerns. This debilitating medical condition can dramatically increase one’s risk for heart disease, cancer, stroke, blood vessel problems, and other chronic medical conditions. Numerous studies found that MOTS-c administration can help treat obesity by improving different health parameters and body processes:

1. MOTS-c may help promote weight loss by reducing the levels of damaging reactive oxygen species during exercise, thereby stimulating physiological adaptation and increased tolerance to exercise. [1-8]
2. A study found that plasma MOTS-c levels were higher in lean but not in obese individuals. [9]
3. In rodents, MOTS-c treatment reduced abdominal fat and inhibited adipogenesis (fat cell formation) through the down-regulation of multiple genes involved in fat cell development. [10]
4. In mice fed with a high-fat diet (60% by calories), MOTS-c treatment prevented diet-induced obesity as well as age-dependent and high-fat diet-induced insulin resistance. [11]
5. In mice, MOTS-c treatment prevented ovariectomy-induced obesity by regulating the production of fat cells. [12]

Improves Blood Sugar Levels and Treats Symptoms of Diabetes

MOTS-c also exerts beneficial effects on blood sugar levels and diabetic symptoms. Studies show that this mitochondrial-derived peptide can help improve the body’s response to insulin hormone:

1. MOTS-c regulates insulin sensitivity, thereby improving the effects of insulin on the body and reducing blood sugar levels. [13]
2. MOTS-c balances blood sugar levels by stimulating cellular glucose uptake. [14]
3. A study reported that reduced activity of MOTS-c was associated with an increased risk of diabetes mellitus. [15]
4. In a postmenopausal animal model, MOTS-c treatment reduced weight gain and insulin resistance. [16]
5. In non-obese diabetic mice, MOTS-c prevented pancreatic islet destruction (insulin-producing cells) by targeting T cells. [17]
6. In diet-induced obese mice, MOTS-c protected against insulin resistance-induced skeletal muscle atrophy (muscle wasting). [18]

Improves Heart Health

Evidence also suggests that MOTS-c can help preserve heart function by combating the detrimental effects of inflammation on the body and that its levels correlate with cardiovascular health:

1. In human subjects, lower circulating MOTS-c levels were associated with impaired coronary endothelial function. [19]
2. In cold-exposed rats, MOTS-c prevented blood vessel dysfunction of the heart. [20]
3. A study found that MOTS-c may help reduce endothelial dysfunction by suppressing inflammatory pathways such as MAPK/NF-κB. [21]
4. In rats, MOTS-c improved myocardial mechanical efficiency and enhanced cardiac systolic function during exercise training. [22]
5. In vitamin D3 plus nicotine-treated rats, injection with MOTS-c at a dose of 5 mg/kg once a day for 4 weeks prevented the deposition of minerals in the heart valves. [23]
6. In a mouse model of gestational diabetes, daily administration of MOTS-c during pregnancy significantly alleviated hyperglycemia (high blood sugar levels), improved insulin sensitivity and glucose tolerance, and reduced the risk of low birth weight and death of offspring. [24]

Fights Bone Loss

The age-related decline in bone mineral density causes osteoporosis and fractures. Studies show that MOTS-c can help correct these problems by improving bone quality and preventing bone-damaging processes:

1. In mice, MOTS-c injection at a dose of 5 mg/kg once a day for 12 weeks alleviated bone loss by inhibiting the process of bone breakdown (osteoclastogenesis). [25]
2. In rats, MOTS-c treatment improved osteoporosis by boosting the production of bone mesenchymal stem cells (BMSCs), which are cells that can transform into bone-forming cells (osteoblasts). [26]
3. A cell study found that MOTS-c treatment protected against osteoporosis by promoting the synthesis of type I collagen in osteoblasts. [27]

Increases Life Expectancy

Aside from correcting obesity and reducing the risk of various chronic debilitating medical conditions, MOTS-c can also increase life expectancy according to studies:

1. A Japanese study found that the mitochondrial m.1382A>C polymorphism which occurs within the MOTS-c DNA sequence was associated with exceptional longevity. [28]
2. A study reported that MOTS-c can help increase life expectancy by promoting cellular homeostasis and preventing metabolic stress. [29]
3. MOTS-c increases the intracellular levels of NAD+ which is a key metabolic coenzyme involved in oxidation-reduction and prevention of age-related diseases. [30-32]
4. In aged human placenta-derived mesenchymal stem cells, MOTS-c promoted homeostasis. [33]
5. In healthy aging men, an increase in muscle MOTS-c with age is consistent with fast-to-slow type muscle fiber transition. [34]

Improves Exercise Tolerance

MOTS-c can also benefit athletes and physically active individuals. Studies show that this mitochondrial-derived peptide can improve exercise tolerance through various important mechanisms:

1. MOTS-c stimulates physiological adaptation and increased tolerance to exercise by reducing the levels of damaging reactive oxygen species during exercise, thereby improving performance and results. [35-36]
2. MOTS-c is actively engaged in transmitting exercise-induced signals to different body organs. [42-48]
3. MOTS-c improves exercise performance by increasing cellular levels of AICAR and activating AMPK – both of these processes boost energy production. [49-51]

Fights Bacterial Infection

Sepsis, a condition characterized by the presence of harmful microorganisms in the blood and uncontrolled inflammatory responses, can be a life-threatening condition. Interestingly, a study found that MOTS-c can treat Methicillin-resistant Staphylococcus aureus (MRSA) infection, which is one of the most hard-to-treat bacterial infections and the major cause of sepsis. [52]

In this study, researchers observed that MOTS-c treatment significantly improved the survival rate and decreased bacteria loads in MRSA-challenged mice. In addition, researchers observed that the treatment significantly reduced the levels of inflammatory substances, suggesting that MOTS-c can be an effective therapeutic option for MRSA infections and other antibiotic-resistant infections.

Associated Side Effects of MOTS-c

MOTS-c side effects are very uncommon. There have been some side effects associated with the use of this peptide wherein the patient had one of the issues listed below at some point while being on MOTS-c. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of MOTS-c. Despite this, it was listed as a side effect associated with MOTS-c even though these associated side effects are very uncommon.

Side effects associated with MOTS-c may include the following:

• Alteration in lipid profiles
• Development of antibodies
• Fluid retention
• High blood sugar
• Stomach upset

References

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