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Can Inhibition of Soluble Epoxide Hydrolase Ameliorate Increased Susceptibility to DSS Induced Colitis in Soybean Oil Fed Mice?
Author(s) -
Deol Sonia Poonamjot,
Yang Jun,
Yu Jacqueline,
Trivedi Amol,
Morisseau Christophe,
Hammock Bruce D.,
Sladek Frances M.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.560.3
Subject(s) - epoxide hydrolase 2 , epoxide hydrolase , chemistry , cytochrome p450 , colitis , enzyme , epoxygenase , biochemistry , endocrinology , medicine , biology , microsome
The incidence of inflammatory bowel disease (IBD) in the U.S. has increased significantly since 1980, preceded by a remarkable increase in the prevalence of soybean oil (SO) in the American diet. Although the role of SO in the etiology of IBD is ambiguous, one of its major components, linoleic acid (LA), is associated with an increased risk of ulcerative colitis (UC). LA is metabolized into oxylipins (also referred to as leukotoxins) via a two‐step reaction involving cytochrome P450 enzymes and the enzyme soluble epoxide hydrolase (sEH). We have recently shown that a diet high in SO (and thus LA) increases the accumulation of oxylipins generated by the cytochrome P450 (CYP)/soluble epoxide hydrolase (sEH) pathway in the liver (PMID: 28970503). Our lab has previously shown that LA decreases the protein levels of the transcription factor hepatocyte nuclear factor 4 alpha (HNF4α) in wild type mouse livers (PMID: 19440305) and that a proper balance of HNF4α isoforms is required for the development and proper functioning of the gut (PMID: 27166517). To investigate the effect of dietary soybean oil on intestinal health, mice were fed either a low‐fat, high fiber vivarium chow diet (Viv) or a high soybean oil plus fiber diet (SO+f) with 19 kcal% LA and the same amount of fiber as Viv. Both male and female C57BL/6N (WT) mice and HNF4α exon‐swap mice (genetically engineered to express just the P1‐form of HNF4α so that in tissues, such as intestine, where both P1 and P2 promoters are active, only HNF4α1/2 is expressed instead of both HNF4α1/2 and HNF4α7/8 (PMID: 16498401)) were put on the diets at weaning. Colitis was induced by Dextran Sodium Sulfate (DSS) treatment eight to nine weeks after weaning. Increased weight loss was observed in both male and female HNF4α (A1HMZ) transgenic mice compared to WT mice, regardless of diet. Differences in other parameters, such as spleen weight, colonic and small intestinal length, that could be attributed to differences in diet and/or HNF4α isoform were also observed. Experiments with an inhibitor of soluble epoxide hydrolase are underway to determine whether soybean oil affects the balance between the HNF4α isoforms via LA diols and whether blocking the production of these oxylipins will make the mice more resistant to DSS induced colitis. Support or Funding Information Supported by CCFA CDA 454808 (P.D.), USDA NIFA Hatch project CA‐R‐NEU‐5680 (F.M.S.), NIEHS grant R01‐ES002710 (B.D.H.), Superfund Research Program P42 ES04699 (B.D.H.). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .