MOLECULAR, CELLULAR, AND REGULATORY ASPECTS OF OBESITY DEVELOPMENT IN CHILDREN
Location: Children Nutrition Research Center (Houston, Tx)
Title: B-vitamin deficiency is protective in experimental colitis
| Benight, Nancy - |
| Stoll, Barbara - |
| Puiman, Patrycja - |
| Bauchart-Thevret, Caroline - |
| Marini, Juan - |
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: April 1, 2010
Publication Date: May 1, 2010
Citation: Benight, N.M., Stoll, B., Puiman, P., Bauchart-Thevret, C., Marini, J., Burrin, D.G. 2010. B-vitamin deficiency is protective in experimental colitis [abstract]. Federation of American Societies for Experimental Biology Conference. 24(1):228.6.
Methionine (Met) cycle activity is critical for normal cell functions and requires B-vitamin (B6/B12) as cofactors. Sadenosylhomocysteine (SAH) is a Met cycle intermediates that is known to inhibit methyltransferases. Met metabolism is altered in patients with inflammatory bowel disease (IBD), but Met’s role in IBD is poorly understood. We hypothesize that accumulation of Met metabolites due to B-vitamin deficiency is protective in experimental colitis. Mice received either a control diet (C), or a B6/B12-deficient diet (D) to disrupt Met metabolism for 2 weeks and were challenged for 5 days with 3% dextran sulfate sodium (DSS) to induce colitis. Clinical and histological disease indices were reduced in D compared to C, along with the colonic expression of the proinflammatory genes (TNF< and iNOS) and myeloperoxidase activity. Whole body Met flux was assessed by infusing 13C-2H3-Met and measuring transmethylation (TM), transsulfuration (TS) and remethylation (RM). Plasma TS was reduced, but RM was increased in D mice. TM was not different between groups. Colonic SAH and plasma Met abundance also were elevated in D mice compared to C. The protective effect of B-vitamin deficiency is associated with reduced inflammation and tissue injury. We postulate that colonic SAH accumulation reduces methyltransferase activity and leads to epigenetic suppression of proinflammatory gene expression.