MOTS-C is a mitochondrial‑derived peptide that activates AMPK‑driven metabolic pathways to enhance glucose uptake, increase fat oxidation, and reduce lipid accumulation in muscle and adipose tissue[1][2]. Preclinical studies demonstrate that daily MOTS-C administration (5 mg/kg i.p. in mice) prevents diet‑induced obesity and insulin resistance[2], while short 7‑day courses restore insulin sensitivity in aged mice to youthful levels. Unlike metformin (which acts primarily in the liver), MOTS-C directly targets skeletal muscle and fat tissues[2]. The peptide also translocates to the nucleus under metabolic stress to regulate nuclear gene expression[4]. Endogenous MOTS-C levels rise sharply with exercise (~12‑fold increase in muscle)[3] and decline with age, suggesting therapeutic potential for age‑related metabolic decline. No formal human clinical trials have been completed to date; current human use is investigational and based on preclinical findings[6].
