VNN2 regulates hepatic steroid synthesis in response to dietary changes.

Abstract

Peroxisome proliferator-activated receptor alpha (PPARα) plays a crucial role in regulating hepatic fat oxidation. Previous studies have identified VNN2 as a potential PPARα target gene in chicken liver. However, the specific function of VNN2 in hepatic lipid metabolism remains unclear. We utilized datasets GSM5764402, GSM5764403, GSE128340, GSE129840, and PRJEB44038 to investigate the expression pattern and potential function of VNN2 in chicken liver. Our analysis included RNA sequencing, qPCR, and triglyceride and total cholesterol assays for verification. Through analysis of single-cell RNA sequencing (scRNA-seq) data, we localized VNN2 expression at the cellular level and identified potential downstream targets of VNN2. We further examined these potential targets in VNN2 overexpressed and knockdown Leghorn male hepatoma (LMH) cells. Our findings revealed that VNN2 is highly expressed in hepatocytes with elevated lipid metabolism and steroid biosynthesis activity. This study confirms that VNN2 promotes steroid biosynthesis by upregulating MSMO1 and FDPS, providing new insights into its role in hepatic lipid metabolism.