MOTS-C 20mg (Mitochondrial-Derived Peptide)

MOTS-c is a short peptide encoded in the mitochondrial genome and a member of the larger group of mitochondrial-derived peptides (MDPs). MDPs have recently been found to be bioactive hormones that play important roles in mitochondrial communication and energy regulation. Originally thought to be related to the mitochondria only, new research has revealed that many MDPs are active in the cell nucleus and that some even make their way into the blood stream to have systemic effects. MOTS-c is a newly identified MDP that has been found to play important roles in metabolism, weight regulation, exercise capacity, longevity, and even processes leading to disease states like osteoporosis. MOTS-c has been found in the nucleus of cells as well as in the general circulation, making it a bonafide natural hormone.

Research in mice indicates MOTS-c can reverse age-dependent insulin resistance in muscles, thereby improving muscle uptake of glucose. It does this by improving skeletal muscle response to AMPK activation, which in turn increases the expression of glucose transporters[1]. This activation is independent of the insulin pathway and thus offers an alternative means of boosting glucose uptake by muscles when insulin is ineffective.

Research in mice has shown that low levels of estrogen lead to increased fat mass and dysfunction of normal adipose tissue. Supplementing mice with MOTS-c increases brown fat function and reduces the accumulation of adipose tissue. It also appears that the peptide prevents adipose dysfunction and inflammation that typically precedes insulin resistance[2].

At least part of the influence that MOTS-c has on fat metabolism is mediated through activation of the AMPK pathway. MOTS-c targets the methionine-folate cycle, increases AICAR levels, and activates AMPK. New research suggests that MOTS-c can actually leave the mitochondria and make its way to the nucleus where it can affect nuclear gene expression. Following metabolic stress, MOTS-c has been shown to regulate nuclear genes involved in glucose restriction and antioxidant responses[3].

Evidence from mice indicates that MOTS-c, particularly in the setting of obesity, is an important regulator of sphingolipid, monoacylglycerol, and dicarboxylate metabolism. By down-regulating these pathways and increasing beta-oxidation, MOTS-c appears to prevent fat accumulation[4].

Research on MOTS-c has led to a new hypothesis about fat deposition and insulin resistance: dysregulation of fat metabolism in mitochondria may result in a lack of fat oxidation, leading to higher levels of circulating fat and forcing the body to boost insulin levels[5].

Research measuring MOTS-c levels in insulin sensitive and insulin resistant individuals has shown that the protein is associated with insulin sensitivity only in lean individuals. Scientists speculate that the peptide may be a useful means of monitoring pre-diabetic lean individuals and that changes in MOTS-c levels could act as an early warning sign of potential insulin insensitivity[6].

MOTS-c appears to play a role in the synthesis of type I collagen by osteoblasts in bone. Research in osteoblast cell lines shows that MOTS-c regulates the TGF-beta/SMAD pathway responsible for the health and survival of osteoblasts[7].

Additional research has revealed that MOTS-c promotes the differentiation of bone marrow stem cells via the same TGF-beta/SMAD pathway, directly leading to increased osteogenesis[8].

Research on MOTS-c has identified a specific change in the peptide that is associated with longevity in certain human populations, such as the Japanese. The change leads to the substitution of a glutamate residue for the lysine normally found in position 14. It is found exclusively in people with Northeast Asian ancestry and is thought to play a role in exceptional longevity[9].

Research measuring MOTS-c levels in humans undergoing coronary angiography has revealed that patients with lower levels have higher levels of endothelial cell dysfunction. Supplementing rats with MOTS-c has been shown to improve endothelial function and improve microvascular and epicardial blood vessel function[10].

Research suggests that at least three MDPs play roles in protecting cardiac cells against stress and inflammation[11].