Metabolomics. 2021 Sep 3;17(9):80. doi: 10.1007/s11306-021-01831-1.
ABSTRACT
INTRODUCTION: A methyl donor depleted (MDD) diet dramatically suppresses intestinal tumor development in Apc-mutant mice, but the mechanism of this prevention is not entirely clear.
OBJECTIVES: We sought to gain insight into the mechanisms of cancer suppression by the MDD diet and to identify biomarkers of cancer risk reduction.
METHODS: A plasma metabolomic analysis was performed on ApcΔ14/+ mice maintained on either a methyl donor sufficient (MDS) diet or the protective MDD diet. A group of MDS animals was also pair-fed with the MDD mice to normalize caloric intake, and another group was shifted from an MDD to MDS diet to determine the durability of the metabolic changes.
RESULTS: In addition to the anticipated changes in folate one-carbon metabolites, plasma metabolites related to fatty acid metabolism were generally decreased by the MDD diet, including carnitine, acylcarnitines, and fatty acids. Some fatty acid selectivity was observed; the levels of cancer-promoting arachidonic acid and 2-hydroxyglutarate were decreased by the MDD diet, whereas eicosapentaenoic acid (EPA) levels were increased. Machine-learning elastic net analysis revealed a positive association between the fatty acid-related compounds azelate and 7-hydroxycholesterol and tumor development, and a negative correlation with succinate and β-sitosterol.
CONCLUSION: Methyl donor restriction causes dramatic changes in systemic fatty acid metabolism. Regulating fatty acid metabolism through methyl donor restriction favorably effects fatty acid profiles to achieve cancer protection.
PMID:34480220 | DOI:10.1007/s11306-021-01831-1