Dietary arachidonic acid-mediated effects on colon inflammation using transcriptome analysis

• Published in: Molecular nutrition & food research Vol. 54; no. S1; pp. S62 - S74
• Main Authors: Knoch, Bianca, Barnett, Matthew P.G, McNabb, Warren C, Zhu, Shuotun, Park, Zaneta A, Khan, Anar, Roy, Nicole C
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.05.2010; WILEY-VCH Verlag; WILEY‐VCH Verlag
• Subjects: administration & dosage; Animals; arachidonic acid; Arachidonic Acid - administration & dosage; Arachidonic Acid - pharmacology; chemically induced; Colitis; colon; Colon - physiopathology; deficiency; Diet; Disease Models, Animal; eicosanoids; fibrosis; Gene Deletion; Gene expression; Gene Expression Profiling; Gene Expression Regulation; gene targeting; genes; genetic markers; genetics; Genotype; Humans; IL10 gene-deficient mice; inflammation; Inflammation - genetics; Inflammation - physiopathology; Inflammatory Bowel Diseases; Inflammatory Bowel Diseases - chemically induced; Inflammatory Bowel Diseases - physiopathology; Interleukin-10; Interleukin-10 - deficiency; Interleukin-10 - genetics; Intestinal Mucosa; Intestinal Mucosa - pathology; Intestinal Mucosa - physiopathology; Male; metabolism; Mice; Mice, Inbred C57BL; mucosa; n-6 Polyunsaturated fatty acid; oleic acid; Oligonucleotide Array Sequence Analysis; oxidative stress; pathology; pharmacology; physiopathology; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Sterol Regulatory Element Binding Protein 1; Sterol Regulatory Element Binding Protein 1 - genetics; transcription factors; transcriptome
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.200900543

Increased levels of n-6 arachidonic acid (AA), a precursor of pro-inflammatory eicosanoids, have been found in the colon mucosa of inflammatory bowel disease patients when compared with healthy subjects. The hypothesis was that dietary AA would aggravate colon inflammation by changing expression of genes in inflammatory signaling pathways. AA-enriched diet was fed to IL10 gene-deficient (Il10⁻ / ⁻) mice, model of a inflammatory bowel disease, and compared with Il10⁻ / ⁻ mice fed an oleic acid control diet. Effects of AA on gene expression profiles during colitis were examined using whole genome microarray analysis. Dietary AA decreased the expression levels of some colonic genes in ER stress, complement system, nuclear respiratory factor 2-mediated oxidative stress and positive acute phase response pathways compared with Il10⁻ / ⁻ mice fed an oleic acid diet. AA increased the expression levels of fatty acid catabolism genes, but decreased that of lipid synthesis genes during colitis, likely by sterol regulatory element binding transcription factor 1 and target gene regulation. A link has been suggested between AA and reduction of intestinal fibrosis by down-regulating the expression levels of pro-inflammatory and fibrotic marker genes. Contrary to the hypothesis, these findings suggest that dietary AA, in the present experimental conditions, is not pro-inflammatory, reduces ER stress and protects colonocytes from oxidative stress in Il10⁻ / ⁻ mice.