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Prostaglandins Leukot Essent Fatty Acids. 2018 Dec;139:14-19. doi: 10.1016/j.plefa.2018.11.001. Epub 2018 Nov 2.

Higher baseline expression of the PTGS2 gene and greater decreases in total colonic fatty acid content predict greater decreases in colonic prostaglandin-E2 concentrations after dietary supplementation with ω-3 fatty acids.

Author information

1
Department of Nutritional Sciences, University of Michigan, Ann Arbor, MI.
2
Department of Family Medicine, University of Michigan, Ann Arbor, MI; Department of Biostatistics, University of Michigan, Ann Arbor, MI.
3
Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
4
Department of Internal Medicine, University of Michigan, Ann Arbor, MI; Department of Pharmacology, University of Michigan, Ann Arbor, MI.
5
Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109.
6
Department of Family and Community Medicine, Penn State University, Hershey, PA.
7
Department of Nutritional Sciences, University of Michigan, Ann Arbor, MI; Department of Family Medicine, University of Michigan, Ann Arbor, MI. Electronic address: Zoralong@umich.edu.

Abstract

This study evaluated whether mRNA expression of major genes regulating formation of prostaglandin (PG)E2 in the colon and colonic fatty acid concentrations are associated with the reduction in colonic mucosal PGE2 after dietary supplementation with omega-3 (ω-3) fatty acids. Supplementation with ω-3 fatty acids was done for 12 weeks using personalized dosing that was expected to reduce colonic PGE2 by 50%. In stepwise linear regression models, the ω-3 fatty acid dose and baseline BMI explained 16.1% of the inter-individual variability in the fold change of colonic PGE2 post-supplementation. Increases in mRNA gene expression after supplementation were, however, modest and were not associated with changes in PGE2. When baseline expression of PTGS1, PTGS2 and HPGD genes was included in the linear regression model containing dose and BMI, only PTGS2, the gene coding for the inducible form cyclooxygenase, was a significant predictor. Higher relative expression of PTGS2 predicted greater decreases in colonic PGE2, accounting for an additional 13.6% of the inter-individual variance. In the final step of the regression model, greater decreases in total colonic fatty acid concentrations predicted greater decreases in colonic PGE2, contributing to an additional 18.7% of the variance. Overall, baseline BMI, baseline expression of PTGS2 and changes in colonic total fatty acids together accounted for 48% of the inter-individual variability in the change in colonic PGE2. This is consistent with biochemical data showing that fatty acids which are not substrates for cyclooxygenases can activate cyclooxygenase-2 allosterically. Further clinical trials are needed to elucidate the factors that regulate the fatty acid milieu of the human colon and how this interacts with key lipid metabolizing enzymes. Given the central role of PGE2 in colon carcinogenesis, these pathways may also impact on colon cancer prevention by other dietary and pharmacological approaches.

KEYWORDS:

Arachidonic acid; Colon cancer; Cyclooxygenase; Cyclooxygenase (COX); Fatty acids; Fish oils; Inflammation; Prostaglandin E(2); eicosapentaenoic acid; prostaglandin E(2) (PGE(2)); ω-3 (EPA); ω-6 (AA)

PMID:
30471768
PMCID:
PMC6343141
[Available on 2019-12-01]
DOI:
10.1016/j.plefa.2018.11.001
[Indexed for MEDLINE]

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