Introduction Previously we reported that lipolysis-stimulated lipoprotein receptor (LSR) mediates the cell proliferation via lipid metabolism in epithelial ovarian cancer (EOC). We newly developed anti-LSR antibody. Anti-LSR antibody showed stronger anti-tumor effect against LSR positive EOC cells, especially in High-Fat Diet (HFD) fed mouse compared to Normal-Diet (ND) fed mouse. That suggests lipid molecules in HFD might contribute to cell proliferation via LSR. In this study, we performed metabolome analysis using each serum of HFD and ND fed mouse. We analyzed the metabolomic profile of lipid molecules.

Methods We established HFD and ND fed mouse and obtained each serum to perform metabolome analysis. We compared the metabolomic profile of HFD and ND fed mouse serum and identified the lipid metabolites which might associate with the cell proliferation. We evaluated the effect on promoting cell proliferation by the lipid molecules and signaling pathway mediated through LSR.

Results Metabolome analysis detected 210 metabolites, and PCA showed obviously different metabolic profiles of HFD serum compared to ND serum. PLS-DA also revealed cholesterol, oleic acid and arachidonic acid as lipid molecules with high VIP score. These molecules significantly promoted the cell proliferation through MAPK signaling pathway (p<0.05).

Conclusion/Implications Metabolome analysis showed that certain lipid molecules contribute cell proliferation of LSR positive EOC.