MOTS-c

ID: motsc

Aliases: mitochondrial-derived peptide MOTS-c, MOTS-C

Type: compound

Route/form: injection in preclinical contexts; no established clinical route

Status: research

Evidence level: preclinical

Best data tier: direct preclinical; human physiology context + human association

Support scope: human, non-human/mechanistic, review/regulatory

Source types: human_association_and_preclinical, human_physiology, preclinical, review

Linked sources: 6

Broad outcomes: Fat loss / metabolic health, Longevity / mitochondrial / redox, Muscle growth / performance / recovery

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• AMPK-related metabolism
• mitochondrial stress signaling

Optimization domains

• metabolic
• mitochondrial
• exercise

Research basis

• Foundational animal work supports metabolic homeostasis, insulin-resistance, and AMPK-linked stress-adaptation hypotheses.
• Human studies show endogenous MOTS-c relates to lipid/insulin physiology and insulin-sensitivity phenotypes, which keeps the target biologically plausible.
• Exercise and skeletal-muscle animal data provide an adjacent mechanism for why MOTS-c is discussed near exercise mimetics and mitochondrial peptides.

Limits, risks, and missing evidence

• Interventional human data for exogenous MOTS-c in fat loss, endurance, or mitochondrial optimization are not robust.
• Endogenous biomarker associations do not prove that injected MOTS-c produces the same physiology.
• Peptide stability, delivery, exposure, and dose translation remain unresolved.

Risk flags

• unapproved context
• limited human data
• human association not causation

Linked papers, labels, and reviews

1. MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance
   preclinical / pubmed_motsc_2015
   Foundational MOTS-c animal/metabolic paper.
2. Lipids and insulin regulate mitochondrial-derived peptide MOTS-c in PCOS and healthy subjects
   human_physiology / pubmed_motsc_human_pcos_lipid_insulin_2019
   Human clamp/intralipid physiology study; circulating MOTS-c responds to lipid and insulin exposure but this is not exogenous MOTS-c treatment.
3. Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individuals
   human_association_and_preclinical / pubmed_motsc_insulin_sensitivity_2018
   Human association study; helps separate endogenous MOTS-c physiology from intervention claims.
4. MOTS-c increases in skeletal muscle following long-term physical activity and improves acute exercise performance after a single dose
   preclinical / pubmed_motsc_exercise_muscle_2022
   Rodent training and acute MOTS-c exercise-performance study with skeletal-muscle mechanism; not a controlled human performance trial.
5. Mitochondrial-derived peptide and metabolic states: systematic review and meta-analysis
   review / pubmed_motsc_meta_2024
   Human association literature, not interventional efficacy.
6. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging
   review / pubmed_motsc_mechanisms_2023
   Mechanistic review covering AMPK, stress-response, exercise, insulin-resistance, inflammation, and aging-related MOTS-c biology.