Lipidomic impacts of an obesogenic diet upon Lewis lung carcinoma in mice

Authors: Sundaram, Sneha; ZACEK, PETR - Former ARS Employee; Bukowski, Michael; Mehus, Aaron; Yan, Lin; Picklo, Matthew

Submitted to: Frontiers in Oncology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/13/2018
Publication Date: 5/11/2018
Citation: Sundaram, S., Zacek, P., Bukowski, M.R., Mehus, A.A., Yan, L., Picklo, M.J. 2018. Lipidomic impacts of an obesogenic diet upon Lewis lung carcinoma in mice. Frontiers in Oncology. 8:134. https://doi.org/10.3389/fonc.2018.00134.
DOI: https://doi.org/10.3389/fonc.2018.00134

Interpretive Summary: Obesity is a risk factor for cancer. Obese cancer patients have poor prognosis, early recurrence, and shorter disease-free intervals compared to patients with normal body weights. In laboratory rodents, obesity results in rapid growth of the primary tumor and enhances spread of cancer cells from the primary tumor to distance organs. Cancer is active in energy metabolism which provides the nutrient needs for its rapid growth and progression. Lipids (components of body fat) play a major role in tumor cell survival and growth leading to cancer progression and metastasis. To understand the roles of obesity in cancer progression, we analyzed lipids in tumors from lean and obese mice fed a standard control diet and a high-fat diet, respectively. We found that tumors from obese mice consuming the high-fat diet had significant alterations in tumor lipid concentrations and compositions. These findings indicate that the altered lipid metabolism by cancer cells may contribute, at least partly, to obesity-enhanced cancer growth and aggression. This study emphasizes the importance of a healthy dietary practice for the health and wellbeing and for the prevention of chronic diseases including cancer.

Technical Abstract: Metabolic reprogramming of lipid metabolism is a hallmark of cancer. Consumption of a high-fat obesogenic diet enhances spontaneous metastasis using a Lewis lung carcinoma (LLC) model. In order to gain further insight into the mechanisms by which dietary fats impact cancer progression, we conducted a lipidomic analysis of primary tumors originated from LLC from mice fed a standard AIN93G diet or a soybean oil-based high-fat (HF) diet. Hierarchical clustering heatmap analysis of phosphatidylcholine (PC) lipids and phosphatidylethanolamine (PE) lipids demonstrated an increase in polyunsaturated fatty acids (PUFA)-containing phospholipids and a decrease in mono-unsaturated fatty acids (MUFA)-containing lipids in tumors from mice fed the HF diet. The quantities of 51 PC and 24 PE lipids differed in LLC tumors derived from mice fed the control and the HF diets. Analysis of tricacylglycerol (TAG) lipids identified differences in 32 TAG (by brutto structure) between the two groups; TAG analysis by neutral loss identified 46 PUFA-containing TAG species that were higher in mice fed the HF diet than in the controls. Intake of the HF diet did not alter the expression of the de novo lipogenesis enzymes (fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1). Our results demonstrate that the dietary fatty acid composition of a HF diet is reflected in the higher order lipidomic composition of primary tumors. Subsequent data are needed to investigate how these lipidomic changes may be used for targeted dietary intervention to reduce tumor growth and malignant progression.