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Free U.S. shipping on orders over $150MOTS-c is a mitochondrial-derived and exercise-induced peptide whose levels decrease with age [1]. It improves insulin sensitivity, glucose metabolism, and metabolic homeostasis [2]. Animal studies suggest that, by activating AMPK, it can mitigate obesity resulting from high-fat diets, aging, and menopause [3, 2]. It also regulates age-related inflammation and various aspects of age-related physical decline, such as bone and muscle losses [1].
In pancreatic cells, MOTS-c lowers insulin secretion and increases glucagon production [4]. In mice with aberrant lipid metabolism, MOTS-c treatment significantly reduced lipid buildup in liver cells [5].
In rodents, high-fat diet-induced obesity can promote insulin resistance and fat accumulation that triggers chronic inflammation. In mice, MOTS-c administration protects against both age-related and high-fat diet-induced insulin resistance, and diet-induced obesity [6].
Hormonal changes during pregnancy can affect insulin sensitivity and cause high blood sugar, leading to gestational diabetes. In pregnant women and mouse models of gestational diabetes, MOTS-c normalized blood sugar, and enhanced insulin sensitivity and glucose tolerance. The MOTS-c treatment lowered both the birth weight-associated complications and mortality of offspring caused by gestational diabetes [7].
Low estrogen during menopause can cause weight gain and fat redistribution in favor of white fats, which increases insulin resistance and the risk of metabolic disorders. In contrast, the more mitochondria-dense brown fats burn more calories, and improve glucose and lipid metabolisms. In ovarectomized mice, MOTS-c increases brown fat activation, and reduces fat accumulation and inflammation in white adipose tissue, which contributes to the lower level of fats in serum and liver [3].
In heart failure, fluid buildup and increased pressure in the lungs can cause lung injury. MOTS-c reduced heart dysfunction and remodeling caused by heart failure and lowered inflammation while boosting antioxidant activity in the hearts of sick mice [8]. It can also prolong injured heart and lung cells’ life cycle [9, 10].
Age-related sarcopenia can reduce overall healthspan and independence, while increasing various metabolic health risks. MOTS-c suppresses myostatin and lipid infiltration that contributes to muscle atrophy, even in immobilized animals [11, 12]. Older adults with higher circulating MOTS-c have better muscle performance and lean mass, while those with lower levels experienced more sarcopenia [13]. In a mouse model of aging, MOTS-c can significantly increase physical performance by activating genes related to skeletal muscle metabolism and myoblast adaptation to metabolic stress [1].
In an in vitro model of muscle development, MOTS-c peptide helps muscle cells to form properly, affecting their integral parts such as myotubes. It supports muscle cell formation at the expense of lipid accumulation while protecting muscle cells from the breakdown effects of inflammatory cytokine IL-6 [14].
Age-related bone loss often parallels muscle loss, and various anti-sacropenic stimuli also protect bone health. Importantly, metabolic dysfunction and inflammation tend to accelerate bone loss. MOTS-c mitigates age-related bone loss by stimulating osteoblasts and suppressing osteoclasts by modulating AMPK and inflammatory responses [15]. In a mouse bone damage model, MOTS-c treatment reduced bone loss and inflammation and prevented the formation of osteoclasts [16].
Sepsis is a potentially lethal condition characterized by systemic overactive immune reactions towards an infection or noninfectious agents. MOTS-c greatly improves survival and lowers bacterial counts in MRSA-infected experimental mice. It also reduces levels of pro-inflammatory cytokines like TNF-α, IL-6, and IL-1β, while increasing the anti-inflammatory cytokine IL-10 [17].
Type 1 diabetes patients have lower endogenous MOTS-c levels than healthy controls. In a mouse model of type 1 diabetes, exogenous MOTS-c prevents pancreatic β cell destruction by shifting CD4+ T cells towards a less self-destructive phenotype, suggesting that MOTS-c may be beneficial as an autoimmune treatment [18].
Age-related inflammation and declining antioxidant capacity are key drivers of aging and related diseases. Older adults aged 70–81 years have 20% less MOTS-c than younger adults 18–30 years old [19]. In a mouse model of type 2 diabetes, MOTS-c administration increased antioxidant enzymes like SOD and CAT, protecting myocardial cells from oxidative stress [20].
Unlike acute pain, neuropathic pain is pain caused by nervous system dysfunction related to nerve damages, rather than by injury or inflammation. MOTS-c’s antinociceptive effects pertain to its ability to restore mitochondrial health, and inhibit microglial and pain signals in the spinal cord [21]. Furthermore, compared to morphine, MOTS-c has far fewer side effects such as gastrointestinal transit inhibition and motor incoordination [22].
Research Use Only. All findings described above are derived from preclinical studies (animal models and in vitro experiments). MOTS-c is not approved by the FDA for any diagnostic or therapeutic use in humans. Genesis Peptides makes no claims regarding human clinical efficacy. This product is sold exclusively for laboratory research.
Every lot undergoes six independent assays before release. Results are published in the lot-specific Certificate of Analysis.
MOTS-c is a mitochondrial-derived peptide encoded within the 12 S rRNA region of mtDNA. It is described as a mitochondrial-derived peptide that regulates metabolic homeostasis and mimics exercise signaling. A review describes MOTS-c as a mitochondrial-derived microprotein (mitokine) encoded within the 12 S rRNA gene that exerts intracrine, paracrine, and endocrine effects across multiple tissues.
MOTS-c is a mitochondrial-derived peptide encoded within the 12S rRNA region of mtDNA. More specifically, it is encoded by the MT-RNR1/12S rRNA open reading frame.
MOTS-c is described as a mitochondrial-derived peptide that regulates metabolic homeostasis and mimics exercise signaling. A review describes MOTS-c, the mitochondrial open-reading frame of the 12S rRNA-c, as a key regulator of cellular metabolism, insulin sensitivity, oxidative stress, and inflammatory responses. MOTS-c is also described as having a well-known anti-oxidative effect.
In diabetic rats, MOTS-c administration reduced immunohistochemical levels of NLRP3, ASC, and cleaved caspase-1 in left ventricular heart tissue. In C26 cachectic mice, MOTS-c attenuated the upregulation of the muscle-wasting markers Atrogin-1 (8.6-fold) and MuRF1 (16-fold). In that C26 mouse work, the cachexia-related changes were also accompanied by increased pFOXO1 (+80%), reduced pFOXO3a (-39%), and partial restoration of PGC-1α protein (+143%). The C26 study used male mice inoculated with Colon-26 carcinoma cells, which were treated with MOTS-c or vehicle.
In animal studies, MOTS-c was reported to inhibit PLA2G4A via the MAPK1-MAPK3-NFKB signaling cascade, thereby reducing LMP and enhancing flap survival. In animals, in vivo overexpression of PLA2G4A (cPLA2) delivered by AAV was used to confirm that MOTS-c enhances autophagy and reduces pyroptosis and LMP by suppressing PLA2G4A phosphorylation.
In an animal study, R13A-MOTS-c activated the Nrf2 signaling pathway, as shown by increased nuclear translocation of Nrf2 and upregulation of its downstream target genes. In the same animal work, the protective effects of R13A-MOTS-c were abolished when LAT1 or Nrf2 was inhibited, or in Nrf2-knockout conditions, suggesting Nrf2 is involved in its effects.
In in vitro uptake assays, R13A-MOTS-c entered cells via LAT1-mediated transport. This was shown by competition with the canonical LAT1 substrates leucine and BCH and by LAT1 knockdown experiments. In animal studies, the protective effects of R13A-MOTS-c were abolished upon LAT1 inhibition, Nrf2 inhibition, or in Nrf2-knockout conditions.
In a human observational study, circulating MOTS-c levels were significantly lower in patients with Hashimoto's thyroiditis compared with healthy controls (p < 0.001). In the same human observational study, multivariable regression analysis identified Hashimoto's thyroiditis (β = -30.04, p < 0.001) and HOMA-IR (β = -0.85, p < 0.001) as independent determinants of reduced circulating MOTS-c levels.
In an observational study of humans, plasma MOTS-c was decreased in patients with atrial fibrillation. In the same study, plasma MOTS-c was inversely correlated with NT-proBNP levels. In an observational study of human atrial tissue, MOTS-c was significantly downregulated in atrial fibrillation tissue. In that tissue study, MOTS-c levels were inversely correlated with the extent of fibrosis.
In a human clinical trial, MOTS-c was measured in plasma by an in-house enzyme-linked immunosorbent assay (ELISA) in individuals with cerebral palsy and typically developing controls, with blood obtained before and 1 h after exercise. In an animal study, serum MOTS-c content was measured using enzyme-linked immunosorbent assay. In a human observational cohort of 150 patients (118 kidney transplant recipients and 32 age-matched controls), serum MOTS-c was measured using a commercial ELISA kit.
MOTS-c is described as a mitochondrial-derived peptide that regulates metabolic homeostasis and mimics exercise signaling. In a human clinical trial, plasma MOTS-c was measured by an in-house enzyme-linked immunosorbent assay in individuals with cerebral palsy and in typically developing controls, before and 1 hour after exercise. The available facts do not report the results of that exercise measurement, so they do not say whether MOTS-c levels changed after exercise.
In a human observational cohort, MOTS-c showed a consistent but nonsignificant trend toward lower risk of allograft loss in competing risk analysis. The reported adjusted sHR was 0.50, with a 95% CI of 0.22-1.10 and p = 0.08. In the same human observational cohort, serum MOTS-c was not associated with all-cause mortality or follow-up eGFR decline.
FOR RESEARCH USE ONLY — Products are sold exclusively for in vitro and preclinical laboratory research. Not for human consumption or administration. Not intended for diagnostic or therapeutic use. These statements have not been evaluated by the FDA.