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MOTS-c Peptide


Active member
Nov 27, 2009
Stuff looks pretty sweet for improving insulin sensitivity.


MOTS‐c is a peptide of 16 amino acids expressed by a mitochondrial gene. Research by Pinchas Cohen and his colleagues at the Leonard Davis School of Gerontology at the University of Southern California provides evidence that mitochondria play a key role in signaling and in energy production.
MOTS-c is known to regulate metabolic functions throughout the body, including turning glucose into usable energy. The first studies on MOTS-c were conducted on obese mice. They showed that the peptide helped boost glucose metabolism even when the mice were fed a high fat diet. These preliminary studies show evidence for improved control over blood sugar levels for those with type 2 diabetes and obesity.
Cohen’s research also shows that skeletal muscle is the major target tissue of MOTS‐c. The skeletal muscle enhances insulin sensitivity and increases glucose uptake in myocytes (muscle cells) by activating the AMPK pathway and at the same time without increasing insulin. He also went on to say that it is fair to call MOTS‐c an exercise‐mimetic, meaning it imitates exercise on the body. Exercise also increases muscle glucose uptake without stimulating insulin.
AMPK (AMP‐activated protein kinase), was identified in 1999 as the master switch for metabolism and the central regulator of both glucose and lipid (fat) metabolism. Since then it has been a target for therapeutic intervention against metabolic conditions such as type‐2 diabetes.

Image via Science Direct


Metabolic flexibility is when our metabolism can efficiently switch and change when metabolic demand or supply is needed. These types of changes have trained our body to manage energy metabolism for optimal substrate (glucose, fatty acids, amino acids) storage and use during states of either food excess or deficiency, and periods of either rest or increased energy demand.
The human body knows how to use moderate amounts of carbohydrates, amino acids and fatty acids. Our western diet, however, is characterized by excess food supply. Metabolic dysfunction or metabolic inflexibility is caused by continuous intake of excess calories, processed foods, and physical inactivity.


In various models of obesity and diabetes we know that some metabolic pathways are dysfunctional. It is caused by competition between sugars, fats and proteins and what we call the 3 prongs of metabolic insensitivity.
  1. Distorted nutrient sensing. This means the cell's ability to recognize and respond to substrates such as sugars or fats isn’t working. Insulin resistance is an example, it’s when cells in your muscles, fat, and liver don't respond well to insulin and can't use glucose from your blood for energy.
  2. Blunted substrate switching. Example: skeletal muscle being unable to switch from carbohydrates to fats for energy needs.
  3. Impaired energy homeostasis. The inability of the body to regulate food intake (energy inflow) and energy expenditure (energy outflow).
Excess calories can overwhelm the mitochondria and cause mitochondrial dysfunction.
This has many detrimental effects on metabolism and is strongly associated with weight gain in both humans and animal models.

Image via Semantic Scholar


A functional metabolism needs proper glucose and insulin regulation, proper energy consumption and usage and optimal mitochondria functioning. Other factors can contribute as well but the more we learn the more we are understanding that the mitochondria may actively regulate metabolic homeostasis at the cellular level. Could we then propose this equation, fix the mitochondria = fix the metabolism?

How MOTS-c Helps​

We know that mitochondria are the main cellular sites devoted to ATP (energy) production and fatty acid oxidation. The Mitochondrial-Derived Peptide MOTS-cpromotes metabolic homeostasis and reduces obesity and insulin resistance. Mitochondria also play a crucial role in determining metabolic flexibility.
MOTS-c in Osteoporosis
Osteoporosis is a multi-factor and age-related metabolic disease. Bone mesenchymal stem cells (BMSCs) are the progenitor cells of osteoblasts and adipocytes and play an essential role in the process of bone formation.
AMPK can stimulate the proliferation, differentiation and mineralization of osteoblasts, which exerts an important role in the cellular functions of osteoblasts. Osteoblasts are cells that make bone. Bone mass is maintained by a balance between the activity of osteoblasts that form bone and other cells called osteoclasts that break it down.
Studies show that BMSC’s treated with MOTS-c upregulated expression levels of ALP, Bglap, and Runx2. This resulted in the formation of mineralized nodules, indicating the osteogenic capacity of BMSC’s regulated by MOTS-c. In simple nonscientific terms,
MOTS-c promotes cell differentiation of BMSCs to osteoblasts = bone formation.


  • Promotes fatty acid metabolism in the liver
  • Promotes metabolic flexibility and homeostasis
  • Helps regulate mitochondrial energy
  • Protects against age and diet dependent insulin resistance and obesity
  • Helps with weight loss
  • Promotes resistance to metabolic stress
  • Improves exercise capacity
  • Helps prevent osteoporosis
  • Improves glucose regulation
  • Promotes cell differentiation to form osteoblasts


MOTS-c, as a mitochondrial signaling peptide, acts on the muscle, activates AMPK, and helps maintain of metabolic flexibility and homeostasis. It also regulates cellular and systemic glucose metabolism and restores insulin sensitivity. It has also been found to promote cell differentiation which results in bone formation.


New member
May 21, 2007
I used it at 10mg every 5 days for about 10 weeks asking with my TRT. I was interested in the effect on my A1C, insulin resistance, and triglycerides. Haven't been to get blood work done, however.

Though the scale didn't move much, my body fat did decrease (Based on pictures, comments from family, and the fact that my clothes started fitting looser) and my energy levels were much better.

Not sure about lasting effects, but I don't seem to be putting any of the fat back on and I'm not gaining weight. But I'm pretty strict with my diet, so that has helped I'm sure.

I got it from a source on the board, and honestly, it was not expensive at all compared to some of these companies charging ridiculous prices for small amounts. I plan on running another 10-15 week cycle later in the year.

For the cost, I think it's worth a go if you're interested. The only negative side I had was a tiny red welt with some itching at the injection site the day of.

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