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MOTS-c is a peptide hormone encoded in the mitochondrial genome. It regulates metabolic homeostasis and enhances physical performance. It is a mitochondria-derived peptide (MDP) that promotes biosynthesis of the endogenous AMP analog AICAR and consequently AMP-activated protein kinase (AMPK). Induces cellular and systemic glucose uptake and improves insulin sensitivity. Shown to prevent diet-induced obesity (DIO) in mice. Potential anti-obesity and anti-aging compound.

MOTS-c targets skeletal muscle and can enhance glucose metabolism. Therefore, MOTS-c plays an important role in the regulation of cardiovascular, diabetes, exercise and longevity. It is a new mitochondrial signaling mechanism and plays a role in regulating intracellular and intercellular metabolism. This substance could triggers the activation of AMPK and accumulation of 5-aminomidazole-4-carboxamide ribonucleotide (AICAR), a known AMPK activator, by inhibiting the folate cycle and de novo purine biosynthesis[1-2].

MOTS-c is reported to be safe in recommended dosages. The side effects of this compound include Injection site pruritus. As with all injections, redness and pain at the injection site may be present. As MOTS-c targets the folate cycle and de novo purine biosynthesis pathways, a depletion of intracellular 5-methyl tetrahydrofolate (5-MTHF) may occur when using MOTS-c protocols.

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[1] Mohtashami Z, et al. MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases. Mohtashami, 2022; 23: 11991.
[2] Zheng Y, et al. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Frontiers in Endocrinology, 2023; 14: 1120533.