Poster Topical Area: Energy and Macronutrient Metabolism
Location: Hall D
Poster Board Number: 536
Objective: Metabolic reprogramming of lipid metabolism is a hallmark of cancer. Diet-induced obesity enhances pulmonary metastasis of Lewis lung carcinoma (LLC) in mice. The objective of this study was to determine the impact of feeding a high-fat, obesogenic diet upon the lipidomic composition of LLC in mice.
Methods: LLC primary tumors were obtained from mice fed a control AIN93G or a high-fat diet (HF) with 16% or 45% of energy from soybean oil, respectively. Four lipid species [phosphatidylcholines (PC), phosphatidylethanolamines (PE), ceramides (CER), and triacylglycerols (TAG)] were quantified using a shotgun mass spectrometry approach.
Results: Concentrations of 51 PCs were different in tumors from mice consuming the two diets. Six of these PCs were increased and two were decreased at least two-fold by the HF diet. Twenty-four PEs were responsive to the different diets; one of them [PE(18:2_20:2)] was two-fold greater in HF tumors than in the controls. The content of CER(d18:1/24:2) was 49% higher and CER(d18:1/24:1) was 33% lower in HF tumors than in the controls. Sixty-two TAG structures ranging from 46:0 to 60:15 were identified, of which 12 were increased and three were decreased at least two-fold by the HF diet. Hierarchical clustering heatmap analysis of PCs and PEs and neutral loss analysis of TAGs showed that polyunsaturated fatty acid (PUFA) lipid species were higher in tumors from mice fed the HF diet and that monounsaturated fatty acid (MUFA) lipids were higher in tumors from the control mice. While there was a reduction in MUFA, there were no changes in de novo lipogenesis enzymes fatty acid synthase, stearoyl-CoA desaturase 1, or acetyl CoA carboxylase 1 in tumors from HF-fed mice compared to the controls.
Conclusion: These results indicate that the lipidomic profile of LLC primary tumor reflects the fatty acid composition of the diet. It suggests that lipidomic alteration of the primary tumor by an obesogenic diet may contribute to the aggressiveness of LLC and its metastasis to the lungs.
This work was supported by the U.S. Department of Agriculture, Agriculture Research Service, Research Project 3062-51000-050-00D.
Grand Forks, North Dakota