MOTS-c primes adrenal cortex metabolism without directly driving steroidogenesis

Summary

Animal study in rats examining MOTS-c in the adrenal cortex. Adult male Wistar rats (n = 16) received continuous MOTS-c (0.1 μmol/24 h) or saline via subcutaneous micro-osmotic pumps for 24 hours, and adrenal tissue was analyzed by qRT-PCR, immunohistochemistry, ELISA, and RNA-sequencing. MOTS-c expression was significantly higher in the zona fasciculata/reticularis than in the zona glomerulosa. Treatment changed adrenal gene expression but did not change classical steroidogenic genes or circulating corticosterone and aldosterone.

Key Findings

• MOTS-c treatment did not alter classical steroidogenic genes or circulating corticosterone and aldosterone levels
• RNA-seq identified 39 differentially expressed genes in adrenal tissue
• Purinergic receptor P2ry4 was upregulated 4.3-fold (P < 0.05); the authors describe it as a novel MOTS-c target that enhances calcium signaling
• Apoc4 was upregulated
• Stress markers Bag3 and Smurf2, mitochondrial carrier Slc25a30, and peroxisomal factor Pex11a were downregulated
• Gene set enrichment analysis showed inhibition of cAMP response, mitophagy, and histone deacetylation pathways, with activation of cell proliferation

Relevance to MOTS-c

Extends MOTS-c research into the adrenal cortex. The authors interpret the gene-expression changes as MOTS-c “priming” adrenocortical cells for later ACTH or stress stimulation without raising baseline hormone output, and suggest it as a possible target for HPA-axis disorders. That interpretation was not tested directly here: this was a single 24-hour infusion in a small group of male rats, and no stimulated hormone response was reported in the abstract.

Citation

Blatkiewicz M, et al. Folia Histochem Cytobiol. 2026;64(1):26-38. doi:10.5603/fhc.110668. PMID: 41811086

See Also

• Parent compound: MOTS-c