title: Westernized high-fat diet accelerates weight loss in dextran sulfate sodium-induced colitis in mice, which is further aggravated by supplementation of heme.
abstract: The Western diet, rich in fat and red meat, predisposes for inflammatory bowel disease (IBD); however, little is known about mechanisms involved. Red meat contains high levels of heme, a well-known inducer of the cytoprotective enzyme heme oxygenase-1 (HO-1). Pharmacological induction of HO-1 ameliorates experimental colitis. We analyzed the effect of a westernized high-fat (HF) diet supplemented with heme on intestinal HO-1 expression and dextran sulfate sodium (DSS)-induced colitis. Mice were fed chow or HF diets for 2 weeks. In the second week, the HF diet was supplemented with or without 0.5 μmol/g heme. Subsequently, the 3 diet groups were given drinking water with or without 4% DSS to induce colitis. Significant body weight reduction was first observed after 4 days in the chow/DSS mice (-5±3%), whereas this was evident already after 2 days (-6±2%) in HF/DSS mice, showing increased weight loss compared to chow/DSS mice in the following days. Heme supplementation further aggravated DSS-induced weight loss in HF mice (-18±4% vs. -7±5% for HF+heme/DSS vs. HF/DSS, P<.01). Heme increased HO-1 expression in the colon epithelium but decreased villin messenger RNA levels, indicating epithelial damage. In contrast, heme did not affect DSS-induced colon shortening and histological scores of epithelial damage and inflammation. A westernized diet accelerates DSS-induced weight loss in mice, which is further aggravated by heme, despite the induction of HO-1 in the colon epithelium. Our data warrant a detailed analysis of the association of (red) meat-containing diets and the development of IBD.
authors.affiliation: Department of Gastroenterology and Hepatology, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. e.m.j.van.der.logt01@umcg.nl
authors.forename: Elise M J
authors.initials: EM
authors.lastname: van der Logt
authors.forename: Tjasso
authors.initials: T
authors.lastname: Blokzijl
authors.forename: Roelof
authors.initials: R
authors.lastname: van der Meer
authors.forename: Klaas Nico
authors.initials: KN
authors.lastname: Faber
authors.forename: Gerard
authors.initials: G
authors.lastname: Dijkstra
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D059305:Diet, High-Fat; D019587:Dietary Supplements; D005260:Female; D006418:Heme / Q000008:administration & dosage* / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D015431:Weight Loss
chemical_list: D012333:RNA, Messenger; D006418:Heme; D016264:Dextran Sulfate; D051547:Heme Oxygenase-1