Source comparison
MOTS-c Mitochondrial Function: Mouse vs Human Evidence
Aged C57BL/6 mice (24 months) 15 mg/kg IP 3×/week for 4 weeks Glucose tolerance restored to young-mouse levels; 27% increase in muscle glucose uptake AMPK-mediated GLUT4 translocation independent of insulin signaling Dosage scaled to human equivalent (1.2 mg/k
This comparison does not assign a generated winner or score.
- Aged C57BL/6 mice (24 months)
- 15 mg/kg IP 3×/week for 4 weeks
- Glucose tolerance restored to young-mouse levels; 27% increase in muscle glucose uptake
- AMPK-mediated GLUT4 translocation independent of insulin signaling
- Dosage scaled to human equivalent (1.2 mg/kg) hasn't been tested in clinical trials
- Diet-induced obese mice (16 weeks HFD)
- 5 mg/kg IP daily for 21 days
- 12% reduction in body weight; improved insulin sensitivity (HOMA-IR reduced 35%)
- Reduced hepatic gluconeogenesis via AMPK inhibition of G6Pase and PEPCK
- Weight loss in humans on GLP-1 agonists shows similar AMPK-independent pathways. Unclear if MOTS-c adds benefit
- Human skeletal muscle cells (in vitro)
- 10 μM for 48 hours
- 2.1-fold increase in glucose uptake; enhanced mitochondrial respiration (OCR +18%)
- Direct AMPK phosphorylation confirmed via Western blot; increased PGC-1α mRNA expression
- In vitro concentration doesn't correspond to achievable plasma levels in vivo. Pharmacokinetics unknown
- Humans (observational, n=14 elderly)
- Endogenous plasma MOTS-c measured at baseline
- Higher baseline MOTS-c correlated with better physical performance (gait speed, grip strength)
- Association only. No intervention or causality established
- No exogenous administration data. We don't know if supplementing MOTS-c in low-baseline individuals reproduces the correlation
- The bottom line: mouse models consistently show metabolic improvements. Glucose handling, insulin sensitivity, exercise capacity. At dosages translating to 1–1.5 mg/kg in humans. Human evidence is limited to correlational data showing that people with higher endogenous MOTS-c have better metabolic health. The critical missing piece is a randomized controlled trial testing whether exogenous MOTS-c administration in metabolically impaired humans produces the same AMPK activation and glucose uptake improvements seen in rodent models.