A mitochondrial-derived peptide, MOTS-c, acts as an insulin sensitizer in vivo — VialBase Research
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- MOTS-c is the first mitochondrial-derived peptide shown to regulate metabolism
- Prevented high-fat-diet-induced obesity and insulin resistance in mice
- Activates AMPK pathway and enhances glucose metabolism
Summary
The discovery paper for MOTS-c as a metabolically active peptide. This Cell Metabolism publication identified MOTS-c as a novel mitochondrial-derived peptide (encoded within the 12S rRNA gene) that regulates metabolic homeostasis. Exogenous MOTS-c prevented obesity and insulin resistance in mice on a high-fat diet.
Key Findings
- MOTS-c identified as a novel 16-amino-acid peptide encoded in mitochondrial DNA
- Exogenous MOTS-c prevented high-fat-diet-induced obesity in mice
- Improved insulin sensitivity and glucose tolerance
- Activated AMPK signaling pathway — a key metabolic sensor
- Enhanced glucose utilization and fatty acid oxidation
- Represents a new class of signaling molecules: mitochondrial-derived peptides (MDPs)
Methodology
In-vitro studies in multiple cell lines showing MOTS-c effects on AMPK activation and glucose metabolism. In-vivo mouse studies: MOTS-c injection (IP) during high-fat diet feeding for up to 8 weeks. Metabolic phenotyping including glucose tolerance tests, insulin tolerance tests, body composition (DEXA), and metabolomics.
Limitations
- Animal study (mice) — metabolic effects need human validation
- Intraperitoneal injection in mice — optimal route for humans unknown
- Chronic dosing effects and long-term safety not established
- MOTS-c is mitochondrially encoded — implications for exogenous administration unclear
- No dose-response characterization in this initial study
Relevance to Content
The foundational MOTS-c paper. Must-cite for any content about MOTS-c. Establishes the metabolic narrative: MOTS-c as a mitochondrial signal that regulates whole-body metabolism. The obesity prevention and insulin sensitization angles are directly relevant to the metabolic health audience. Connects to the broader “mitochondrial health” trend.
See Also
- Parent compound: MOTS-c