Lipidomic Profiling Reveals Stage-Associated Triglyceride Accumulation in Macrophages in a Mouse Model of Ovarian Cancer.

Background/

Objectives

Tumor-associated macrophages (TAMs) are critical mediators for immunosuppressive ovarian tumor microenvironments. However, the lipid metabolic features of macrophages at different stages of ovarian tumor development remain poorly understood.

Methods

Here, we performed LC-MS-based lipidomic profiling of CD11b+/F4/80+ macrophages isolated from ID8 tumor-bearing C57/BL6 mice at Days 10, 40, and 80 following tumor cell inoculation.

Results

Principal component analysis and hierarchical clustering revealed stage-associated differences in macrophage lipid profiles. Phosphatidylethanolamine (PE), phosphatidylserine (PS), and lysophosphatidylcholine (LPC) were relatively more abundant at earlier time points, whereas triglyceride (TG) species were more abundant in macrophages isolated at Day 80. Detailed analysis revealed an increased abundance of TG species with greater total numbers of double bonds at Day 80. Pathway analysis identified enrichment of glycerolipid metabolism at Day 80. Consistent with these lipidomic findings, macrophages at Day 80 exhibited increased expression of lipogenic regulators, including Fasn, Pparg, and Srebp1, together with a gene expression profile associated with a pro-tumoral macrophage state. Supplementation of oleic acid to macrophages increased expression of selected genes associated with this macrophage state, supporting a potential relationship between altered lipid metabolism and macrophage gene expression changes.

Conclusions

These findings identify stage-associated TG accumulation and alterations in macrophage lipid metabolism and provide a basis for future studies to determine whether macrophage lipid metabolism contributes to a pro-tumoral macrophage state.