Fatty acid metabolism and colon cancer protection by dietary methyl donor restriction.

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.

• Authors: Oladimeji Aladelokun, Matthew Hanley, Jinjian Mu, John C Giardina, Daniel W Rosenberg, Charles Giardina
• Journal: Metabolomics : Official journal of the Metabolomic Society (Metabolomics) Vol. 17 Issue 9 Pg. 80 (09 03 2021) ISSN: 1573-3890 [Electronic] United States
• PMID: 34480220 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2021. The Author(s).

Chemical References

• Fatty Acids
• Arachidonic Acid

Topics

• Animals
• Arachidonic Acid
• Colonic Neoplasms (prevention & control)
• Diet
• Fatty Acids
• Lipid Metabolism
• Mice