Integrated Multi-Omics Analysis Reveals Dysregulated Lipid Metabolism as a Novel Mechanism in Androgenetic Alopecia

Background and Aims: Androgenetic alopecia (AGA) represents the most prevalent multifactorial condition leading to hair loss, necessitating an enhanced molecular understanding. The aim of this study is to present the analysis integrating protein, mRNA and miRNA between frontal and occipital regions of patients with androgenetic alopecia (AGA) and to identify potential mechanism. Methods and Results: Paired frontal and occipital scalps from four male donors with AGA were collected for transcriptomic and proteomics analyses. The molecular and protein characteristics of AGA were demonstrated by a comprehensive bioinformatics approach. Additionally, immunofluorescence (IF) and dual-luciferase reporter (DLR) assays were employed to confirm the analytical findings. A total of 758 differentially expressed proteins (DEPs), 1802 differentially expressed mRNAs (DERs) and 61 differentially expressed miRNAs (DEmiRNAs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed significant enrichments in lipid metabolism, especially those involving PPAR signaling. Co-expression analyses further supported the association of up-regulated genes with lipid metabolism. A protein-protein interaction network analysis, supplemented by KEGG enrichment and the MCE algorithm, pinpointed four candidate genes: DBI, ACAA1, IDH1 and PEX3. IF confirmed significant upregulation of ACAA1 and PEX3 in scalp tissues with AGA, while IDH1 was downregulated and DBI without significant changes. A competing endogenous RNA network indicated that hsa-miR-1343-3p targets ACAA1 and hsa-miR-3609_R-2 targets IDH1, which were confirmed by DLR assays. Conclusions: This study provides preliminary evidence that hsa-miR-1343-3p-mediated regulation of ACAA1 contributes to AGA pathogenesis, suggesting a link between AGA and lipid metabolism.