Regulation of alternative splicing of retinol metabolism in lipid abnormality of PCOS liver by Cyp4a32 and Hsd17b6.

Liver lipid disorders are common in polycystic ovary syndrome (PCOS) patients. A DHEA-induced PCOS mouse model exhibited elevated liver triglyceride (TG) and total cholesterol (TC), reinforcing this association between liver lipids and PCOS. Liver transcriptomic sequencing revealed that 168 differentially expressed genes and 285 alternative splicing (AS) event genes, significantly enriching retinol metabolism. Further combined analyses showed the Cyp4a32 and Hsd17b6 genes were abnormally expressed in the livers of PCOS mice. AS analysis revealed that Cyp4a32 had upregulated exon skipping (SE), including SE and mutually exclusive exons (MXE), while among the modes of SE, MXE, and alternative 3' splice site (A3SS), Hsd17b6 showed downregulated MXE. These findings suggest that Cyp4a32 and Hsd17b6 may change the retinol metabolism by modulating AS patterns, which then dysregulate hepatic lipid metabolism in PCOS. This study highlights potential therapeutic targets for PCOS-associated liver lipid disorders.