Exploring the potential mechanisms of OSBPL3 in metabolic dysfunction-associated steatotic liver disease by integrating bulk and single-cell RNA sequencing data.

OSBPL3 is vital for fatty liver disease, but its immune mechanisms in metabolic dysfunction-associated steatotic liver disease (MASLD) are unclear. This study investigates these mechanisms for MASLD treatment insights. MASLD datasets from public databases were used. OSBPL3 expression was analyzed by t-test in GSE57425, and its function explored via GSEA. Key cell types were identified in GSE129516 by scRNA-seq, followed by cell-to-cell communication and pseudo-temporal analyses. OSBPL3 expression differed significantly between high-fat and normal diet groups (P = .00048). It was enriched in the "oxidative phosphorylation" pathway, hinting at its role in energy metabolism and mitochondrial function in MASLD. Thirteen cell types were identified, with macrophages and monocytes as key types due to expression and cell percentage differences. Macrophages showed closer communication with granulocytes, fibroblasts, and erythrocytes in nonalcoholic steatohepatitis (NASH) diet samples. Macrophage and monocyte differentiation had 9 distinct states, with OSBPL3 highly expressed during metaphase. This study identified macrophages and monocytes as key cell types in OSBPL3's mechanism in MASLD, offering valuable insights for targeted therapies.