Metabolic
MOTS-c
Mitochondria-derived peptide studied in animal models of metabolism and exercise.
Where the evidence comes from
60 verified records from 16 countries. The number of studies or countries is not proof that MOTS-c works or is safe.
Animal study: 34 · Narrative review: 15 · Human clinical trial: 3 · Other: 2 · Observational human study: 5 · Randomized clinical trial: 1
What is known
Editorial summary not yet written.
What remains uncertain
Editorial summary not yet written.
Conflicting findings
Editorial summary not yet written.
U.S. regulatory status (FDA)
Compound
Product or formulation
FDA status
FDA-approved branded drug
Approved indication
Metara availability (compounded formulation)
Research material (research use only)
Source
Last verified
Notes
Approval applies only to the exact finished drug, formulation and indication. A shared active ingredient does not make a compounded version, blend or other use FDA-approved. Pharmacy or research-material availability is not FDA approval.
International regulatory status
Kept separate from U.S. status. The regulator's country is not the same as where studies took place.
No sourced international decisions recorded yet.
Continue your research
These are two different pathways, not two ways to get the same thing. Neither changes the FDA status shown above.
Clinical care
Available through Metara Health
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EXPLORE BIONEX →Limitations
Evidence is largely from mouse and cell studies.
Human clinical evidence (9)
A Phase 2a, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of MOTS-c (a Mitochondrial-Derived Peptide) in Adults With Prediabetes and Overweight/Obesity
Hudson Biotech · ClinicalTrials.gov · NCT07505745
This recruiting human trial is testing whether investigational MOTS-c improves the body’s response to insulin compared with placebo in adults with prediabetes and overweight or obesity. Safety is also being monitored; no results are reported.
Comparison of the Effects of General Anesthesia and Combined Spinal-Epidural Anesthesia on Ferroptosis, Humanin and MOTS-c Levels in Renal Transplantation: A Prospective Controlled Study
University of Gaziantep · ClinicalTrials.gov · NCT07678073
This human trial compares general anesthesia with combined spinal-epidural anesthesia in adult kidney transplant recipients. It will measure markers of iron-related cell death, humanin and MOTS-c levels, and early transplant outcomes. The trial is recruiting, and no results are reported.
Repeated Heat Stress Modulates the Levels of the Mitokines MOTS-C and FGF21 in Active Men during Calf Muscle Immobilization
Elhusseiny R, Ihsan M, Labidi M, Alhammoud M, Mtibaa K, Nader N, Nasir N, Farooq A, Papakostas E, Olory B, Cruz F, D'Hooghe P, Racinais S, Deldicque L · Medicine and science in sports and exercise · DOI 10.1249/mss.0000000000003825
This human trial compared repeated heat exposure with sham treatment in physically active men whose ankle was immobilized. Heat exposure increased circulating MOTS-c and decreased FGF21 in skeletal muscle, while immobilization itself did not change these signals. Immobilization reduced calf muscle size; the abstract does not establish that heat exposure prevented this loss.
Impact of Radiation Therapy on Serum Humanin and MOTS-c Levels in Patients with Lung or Breast Cancer
Kavak AG, Karslioglu I, Saracaloglu A, Demiryürek S, Demiryürek AT · Current radiopharmaceuticals · DOI 10.2174/0118744710254730231114181358
This observational human study measured MOTS-c and humanin in people with lung or breast cancer before, during, and after radiotherapy. Lung cancer patients had higher MOTS-c levels, which rose further with radiotherapy; breast cancer patients had lower humanin levels. Radiotherapy changed MOTS-c levels in lung cancer patients but not breast cancer patients.
The Mitochondrial-Derived Peptide MOTS-c May Refine Mortality and Cardiovascular Risk Prediction in Chronic Hemodialysis Patients: A Multicenter Cohort Study
Bolignano D, Greco M, Presta P, Duni A, Zicarelli M, Mercuri S, Pappas E, Lakkas L, Musolino M, Naka KK, Misiti R, Foti DP, Andreucci M, Coppolino G, Dounousi E · Blood purification · DOI 10.1159/000540303
This observational human study examined blood MOTS-c levels as a risk marker in people receiving long-term hemodialysis. Higher levels were independently associated with the combined outcome of death or nonfatal cardiovascular events, and adding MOTS-c improved prediction models. Larger, more varied studies are needed to confirm how broadly these findings apply.
Circulating levels of MOTS-c in patients with breast cancer treated with metformin.
Cuyàs E, Verdura S, Martin-Castillo B, Menendez JA · Aging · DOI 10.18632/aging.204423
This randomized human study measured blood MOTS-c in patients with HER2-positive breast cancer receiving chemotherapy and trastuzumab, with or without metformin. Neither regimen significantly changed circulating MOTS-c. Changes also did not differ significantly according to whether patients achieved a complete pathological response, regardless of metformin use.
The Effect of GLP-1 Agonist, SGLT2 Inhibitor and Their Combination on Endothelial Function, Arterial Stiffness and Left Ventricular Deformation in Patients With Type 2 Diabetes With High Cardiovascular Risk
University of Athens · ClinicalTrials.gov · NCT03878706
This human observational study will compare blood vessel and heart function across diabetes medication groups in people with type 2 diabetes and high cardiovascular risk or heart failure with preserved pumping function. The study is recruiting, and no results are reported.
Cohort of Universal Newborn Deafness-gene Screening in Nantong City, China
Affiliated Hospital of Nantong University · ClinicalTrials.gov · NCT06133946
This human observational study follows newborn genetic and hearing screening in Nantong, China, with ongoing follow-up of children with hearing loss. The record lists the study as active but not recruiting, and the abstract reports no results.
Systematic & narrative reviews (15)
MOTS-c in sepsis-induced cardiomyopathy: Mechanisms and translational potential
Zhao Z, Chen W, Zheng X, Geng Z, Dai N, Zhang H, Fu B, Fu X · European journal of pharmacology · DOI 10.1016/j.ejphar.2026.179261
This review examines whether MOTS-c could be relevant to heart muscle dysfunction caused by sepsis, drawing partly on research in other disease models. Studies link MOTS-c to processes involving energy regulation, inflammation, and cell protection, but direct evidence in sepsis-related heart dysfunction is limited. Its potential as a biological marker or treatment candidate remains insufficiently validated.
MOTS-c: How a secreted mitochondrial microprotein may become a potential treatment for inflammatory lung diseases
Amado CA, Agüero J, García-Unzueta M, Berja A, Lavín BA, Martín-Audera P · Journal of translational medicine · DOI 10.1186/s12967-026-08398-2
This review examined MOTS-c in respiratory diseases using human studies and preclinical laboratory and animal research. Available studies suggest lower circulating MOTS-c in acute respiratory distress and chronic respiratory diseases, while administered MOTS-c reduced lung injury in preclinical models. Further clinical studies are needed to establish whether it can affect disease progression or outcomes in people.
MOTS-c in type 2 diabetes mellitus: From risk factors to cardiac complications and potential treatment
Fang T, Han JC, Taberner A, Pham T · Life sciences · DOI 10.1016/j.lfs.2025.124009
This review examines MOTS-c in relation to type 2 diabetes risk factors and complications, including preclinical studies of metabolic disease. Emerging evidence suggests that insufficient MOTS-c production may contribute to diabetes and its complications. The review explores its potential to protect against diabetes-related heart muscle disease, rather than establishing effectiveness in humans.
MOTS-c Functionally Prevents Metabolic Disorders.
Gao Y, Wei X, Wei P, Lu H, Zhong L, Tan J, Liu H, Liu Z · Metabolites · DOI 10.7150/thno.78718
This review summarized genes and cellular pathways linked to MOTS-c in metabolic disorders; the abstract does not specify the study populations. It describes potential effects on insulin resistance, obesity, muscle function, and other processes, mainly through a cellular energy-sensing pathway called AICAR–AMPK. Diagnostic and treatment applications are presented as future possibilities.
MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation.
Zheng Y, Wei Z, Wang T · Frontiers in Endocrinology · DOI 10.3389/fendo.2023.1120533
This review examines how MOTS-c, a peptide made by mitochondria, affects cellular stress responses and metabolism; the abstract does not specify the species underlying the findings. It reports improved glucose metabolism in skeletal muscle and declining levels with age. The authors state that no effective method for clinical use has been developed.
Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases.
Kong BS, Lee C, Cho YM · Diabetes & metabolism journal · DOI 10.4093/dmj.2022.0333
This review examines MOTS-c research in type 1 and type 2 diabetes; the abstract does not specify the study populations or experimental models reviewed. It describes mitochondrial peptides as associated with regulation of cell metabolism and insulin action, and suggests that understanding MOTS-c may inform future therapies.
Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging.
Wan W, Zhang L, Lin Y, Rao X, Wang X, Hua F, Ying J · Journal of translational medicine · DOI 10.1186/s12967-023-03885-2
This review examines MOTS-c in stress responses, metabolism, and aging; the abstract does not specify the populations or experimental models reviewed. It describes MOTS-c moving into the cell nucleus during stress or exercise and regulating stress-adaptation genes. The authors highlight its potential role in maintaining energy balance and supporting healthy aging.
Role of MOTS-c in the regulation of bone metabolism
Yi X, Hu G, Yang Y, Li J, Jin J, Chang B · Frontiers in physiology · DOI 10.3389/fphys.2023.1149120
This review examines MOTS-c research involving bone-forming and bone-resorbing cells. It reports that MOTS-c promotes bone-forming cell growth, development, and mineral deposition while inhibiting the production of bone-resorbing cells. Exercise increases MOTS-c expression, but how this influences bone regulation remains unclear.
Laboratory, animal & other research (36)
MOTS-c preserves mitochondrial subpopulation bioenergetics and genome integrity to attenuate cardiac ischemia reperfusion injury
Santhanam SS, Jayaraman S, Rajesh SS, Iyer VNH, Kurian GA · Molecular biology reports · DOI 10.1007/s11033-026-12064-7
This lab study used isolated female rat hearts to examine injury caused by stopping and restoring blood flow. MOTS-c was associated with improved recovery of heart function, reduced oxidative stress, and partial preservation of mitochondrial function and DNA. The researchers noted that the underlying signaling mechanisms need further validation.
Mitochondrial peptide MOTS-c suppresses systemic and cardiac inflammasome activation in a diabetic rat model
Mills AR, de Souza A, Pham T, Mugisho OO · Experimental physiology · DOI 10.1113/ep093714
This animal study tested MOTS-c in rats with experimentally induced type 2 diabetes. MOTS-c significantly reduced fasting blood sugar and circulating C-reactive protein, an inflammation marker, and reduced markers of an inflammation-activating protein complex in heart tissue. These results concern rats, not demonstrated cardiovascular benefits in humans.
Exogenous MOTS-c mitigates myocardial ischemia-reperfusion injury: experimental and in silico evidence from rat heart models
Santhanam SS, Jayaraman S, Kurian GA · Naunyn-Schmiedeberg's archives of pharmacology · DOI 10.1007/s00210-026-05018-0
This animal laboratory study tested MOTS-c in isolated rat hearts injured by interrupted and restored blood flow, with supporting computer modeling. MOTS-c reduced heart tissue damage, improved heart function, and strengthened antioxidant defenses while reducing markers of inflammation and cell death. The isolated-heart findings require further research before application to humans.
Therapeutic Effects of MOTS-c in the Valproic Acid-Induced Autism Model in Rats: Role of Tetrahydrobiopterin and Brain-Derived Neurotrophic Factor
Güvenir Seven S, Sahin H, Erkanlı Şentürk G, Uysal N, Uzun H, Ekici O, Rakıcı G, Şimşek G · Molecular neurobiology · DOI 10.1007/s12035-026-05741-y
This animal study tested MOTS-c in a valproic acid-induced rat model of autism. MOTS-c reversed impaired sociability, repetitive behaviors, cerebellar cell loss, and increased oxidative stress, but not anxiety or neocortical damage. Blood levels of tetrahydrobiopterin and brain-derived neurotrophic factor did not significantly change, suggesting the observed benefits were independent of changes in these factors.
A mitochondrial-derived peptide MOTS-c contributes to the protective effect against brain injury associated with LPS-induced sepsis by strengthening the blood-brain barrier's ultrastructure
Bai Y, Wu H, Wang X, Guo Y, Gong B, Dong B, Yu Y · The International journal of neuroscience · DOI 10.1080/00207454.2025.2542883
This animal study tested MOTS-c in mice with experimentally induced sepsis. MOTS-c improved survival, reduced brain injury and inflammation, and reduced leakage through the blood-brain barrier, which helps protect the brain.
MOTS-c Protects Against Acetaminophen-induced Liver Injury through the MAPK Signaling Pathway
Li N, Xu Y, Chen Q, Jiang J, Li WW · Protein and peptide letters · DOI 10.2174/0109298665430028251230103831
This animal study tested MOTS-c in male mice with acetaminophen-induced liver injury. MOTS-c reduced liver damage, markers of liver injury, inflammation, oxidative stress, and liver cell death. The researchers linked these protective effects to suppression of the MAPK signaling pathway.
MOTS-c primes adrenal cortex metabolism without directly driving steroidogenesis
Blatkiewicz M, Kaminski K, Sobalska-Kwapis M, Szyszka M, Olechnowicz A, Jopek K, Rucinski M · Folia histochemica et cytobiologica · DOI 10.5603/fhc.110668
This animal study examined how MOTS-c affects adrenal glands in adult male rats. MOTS-c changed metabolic and cell-signaling pathways without changing key hormone-production genes or circulating corticosterone and aldosterone. The researchers concluded that it prepares adrenal cells for later stimulation rather than directly increasing baseline hormone production.
MOTS-c attenuates hyperoxia-induced neonatal cardiac injury by inhibiting oxeiptosis via maintaining the KEAP1-PGAM5 interaction
Li SH, Chen SQ, Lu T, Wang JH, Wang JX, Wu YX, Pang QF, Chen D · Life sciences · DOI 10.1016/j.lfs.2026.124452
This animal and lab study tested MOTS-c in newborn mice and rat heart cells exposed to excessive oxygen. MOTS-c reduced heart enlargement, scarring, and dysfunction in mice and inhibited oxidative stress-related cell death. The findings suggest that MOTS-c could interact with KEAP1 to maintain its interaction with PGAM5, helping limit this cell-death pathway.
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Profile last reviewed September 26, 2026. Educational content only. Not medical advice, a dosing protocol or a treatment recommendation.