Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors |
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| Affiliation: | 1. Department of Family Medicine, University of Michigan, Ann Arbor, MI 48109, USA;2. Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA;3. Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA;4. Department of Statistics, University of Michigan, Ann Arbor, MI 48109, USA;5. Department of Michigan Metabolomics Resource Center, University of Michigan, Ann Arbor, MI 48109, USA;6. Department of Biochemistry, University of Michigan, Ann Arbor, MI 48109, USA;7. Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA;1. Food for Life, Organization for Interdisciplinary Research Projects, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan;2. Animal Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan;1. INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France;2. Clermont Université, Université d''Auvergne, Unité de Nutrition Humaine, BP 321, Laboratoire de Nutrition Humaine, 58 rue Montalembert, F-63009 Clermont-Ferrand, Cedex 1, France;3. CRNH Auvergne, F-63000 Clermont-Ferrand, France |
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| Abstract: | Dietary fish oils have potential for prevention of colon cancer, and yet the mechanisms of action in normal and tumor colon tissues are not well defined. Here we evaluated the impact of the colonic fatty acid milieu on the formation of prostaglandins and other eicosanoids. Distal tumors in rats were chemically induced to model inflammatory colonic carcinogenesis. After 21 weeks of feeding with either a fish oil diet containing an eicosapentaenoic acid/ω-6 fatty acid ratio of 0.4 or a Western fat diet, the relationships between colon fatty acids and prostaglandin E2 (PGE2) concentrations were evaluated. PGE2 is a key proinflammatory mediator in the colon tightly linked with the initiation and progression of colon cancer. The fish oil vs. the Western fat diet resulted in reduced total fatty acid concentrations in serum but not in colon. In the colon, the effects of the fish oil on fatty acids differed in normal and tumor tissue. There were distinct lipodomic patterns consistent with a lipogenic phenotype in tumors. In tumor tissue, the eicosapentaenoic acid/arachidonic acid ratio, cyclooxygenase-2 expression and the mole percent of saturated fatty acids were significant predictors of inter-animal variability in colon PGE2 after accounting for diet. In normal tissues from either control rats or carcinogen-treated rats, only diet was a significant predictor of colon PGE2. These results show that the fatty acid milieu can modulate the efficacy of dietary fish oils for colon cancer prevention, and this could extend to other preventive agents that function by reducing inflammatory stress. |
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