Lipid Metabolomics Analysis of a Rosacea Animal Model Induced by Demodex Mite Extract.

OBJECTIVE

The contribution of Demodex folliculorum to rosacea pathogenesis was investigated using a murine model.

METHODS

Mite-derived proteins were extracted following collection via adhesive tape. A rosacea mouse model was established, and mice received intradermal injections at identical dorsal sites with Cathelicidin antimicrobial peptide LL-37 (LL-37) group, Demodex protein extract (extract group), a combination of LL-37 and extract (mixed group), or phosphate-buffered saline (PBS group). On day 17 post-injection, lesional skin was harvested for hematoxylin and eosin (H&E) staining, lipidomic profiling, and western blotting.

RESULTS

HE staining showed that lymphocyte infiltration and increased adipocytes were observed in the extract group, LL-37 group, and combination group. Lipid metabolomics identified 2604 differential metabolites. Triglyceride (TG) 24:5/16:0/18:1, Monoglyceride (MG) 18:4, MG (19:4), and Phosphatidylcholine (PC) 44:6e were significantly increased in the extract group, LL-37 group, and combination group. Glycerophospholipid metabolism and thermogenesis pathways were enriched in the extract group, LL-37 group, and combination injection group, with the most significant enrichment in the combination injection group. The protein expression levels of Phosphorylated AKT (P-AKT) and Phosphorylated FOXO1 (P-FOXO1) were highest in the combination injection group.

CONCLUSION

Demodex mites promote the upregulation of P-AKT and P-FOXO1 by synergistically activating the Phosphoinositide 3-Kinase (PI3K)-AKT-FOXO1 pathway, which enhances lipid synthesis, leads to lipid metabolism disorders and skin barrier damage, thereby exacerbating the progression of rosacea.