MOTS-c establishes steroidogenic readiness in adrenal tissue — P2ry4 upregulation and metabolic priming — VialBase Research
MOTS-c regulates cellular metabolism through AMPK and mTOR signaling
- MOTS-c regulates cellular metabolism through AMPK and mTOR signaling
- Exerts protective effects across multiple endocrine tissues
- MOTS-c treatment upregulated purinergic receptor P2ry4 (4.3-fold)
- Did not alter classical steroidogenic genes or circulating corticosterone/aldosterone
- Suggests MOTS-c establishes metabolic readiness rather than directly activating hormone synthesis
- 39 differentially expressed genes identified by RNA-seq
- Downregulation of stress markers Bag3 and Smurf2
Summary
Novel study investigating MOTS-c’s role in adrenal physiology using Wistar rats. Adult male rats (n=16) received continuous MOTS-c (0.1 μmol/24h) or saline via subcutaneous micro-osmotic pumps for 24 hours. Adrenal tissues were analyzed using qRT-PCR, immunohistochemistry, ELISA, and RNA-sequencing. MOTS-c showed higher expression in zona fasciculata/reticularis vs. zona glomerulosa.
Key Findings
- MOTS-c treatment did not alter classical steroidogenic genes or circulating hormones
- RNA-seq identified 39 differentially expressed genes in adrenal tissue
- Notable upregulation of purinergic receptor P2ry4 (4.3-fold, P < 0.05) — a novel MOTS-c target
- P2ry4 upregulation enhances calcium signaling
- Upregulation of Apoc4 (apolipoprotein — cholesterol transport for steroidogenesis)
- Downregulation of stress markers Bag3 and Smurf2
- Downregulation of mitochondrial carrier Slc25a30 and peroxisomal factor Pex11a
- Supports “steroidogenic readiness” hypothesis — MOTS-c primes metabolic pathways without directly activating hormone synthesis
Relevance to MOTS-c
Expands understanding of MOTS-c beyond metabolic/exercise biology into endocrine physiology. The finding that MOTS-c primes adrenal tissue for steroidogenesis without directly activating it suggests a nuanced regulatory role. The P2ry4 upregulation is a novel target that connects MOTS-c to calcium signaling in endocrine tissues. Important for understanding MOTS-c’s whole-body effects.
Citation
Blatkiewicz M, et al. Histochem Cell Biol. 2026. PMID: 41811086
See Also
- Parent compound: MOTS-c