Lysophosphatidylcholine induces expression of genes involved in cholesterol biosynthesis in THP-1 derived macrophages

Lysophosphatidylcholine (LPC), a major component of oxidized low-density lipoprotein, is associated with atherosclerosis, obesity, stroke, and cancer. However, the direction and mechanism of this relationship remains unclear. In this study, we conducted RNA profiling in THP-1 derived macrophages treated with LPC and uncovered a relationship between LPC and the cholesterol biosynthesis pathway. Principal component analysis (PCA) of RNA profiling showed that untreated THP-1 cells and those treated with 10, 20, or 40 µM LPC were distinctly distributed. Functional annotation revealed that LPC affected the expression of genes involved in cytokine-cytokine receptor interaction, TNF signaling, and MAPK signaling. Interestingly, LPC also altered the expression of 11 genes involved in cholesterol synthesis such as those in terpenoid backbone biosynthesis and steroid biosynthesis pathways. This increased gene expression occurred in a dose-dependent manner in response to LPC treatment. Especially, LPC with saturated acyl groups enhanced the expression of these genes compared to LPC with unsaturated acyl groups, and similar results were shown in response to saturated and unsaturated free fatty acids. Our findings demonstrate that LPCs with saturated acyl groups induce the expression of genes involved in cholesterol biosynthesis and may have implications for cholesterol related diseases.