title: High fat diet accelerates pathogenesis of murine Crohn's disease-like ileitis independently of obesity.
abstract: BACKGROUND
  Obesity has been associated with a more severe disease course in inflammatory bowel disease (IBD) and epidemiological data identified dietary fats but not obesity as risk factors for the development of IBD. Crohn's disease is one of the two major IBD phenotypes and mostly affects the terminal ileum. Despite recent observations that high fat diets (HFD) impair intestinal barrier functions and drive pathobiont selection relevant for chronic inflammation in the colon, mechanisms of high fat diets in the pathogenesis of Crohn's disease are not known. The aim of this study was to characterize the effect of HFD on the development of chronic ileal inflammation in a murine model of Crohn's disease-like ileitis.
  
  
  METHODS
  TNF(ΔARE/WT) mice and wildtype C57BL/6 littermates were fed a HFD compared to control diet for different durations. Intestinal pathology and metabolic parameters (glucose tolerance, mesenteric tissue characteristics) were assessed. Intestinal barrier integrity was characterized at different levels including polyethylene glycol (PEG) translocation, endotoxin in portal vein plasma and cellular markers of barrier function. Inflammatory activation of epithelial cells as well as immune cell infiltration into ileal tissue were determined and related to luminal factors.
  
  
  RESULTS
  HFD aggravated ileal inflammation but did not induce significant overweight or typical metabolic disorders in TNF(ΔARE/WT). Expression of the tight junction protein Occludin was markedly reduced in the ileal epithelium of HFD mice independently of inflammation, and translocation of endotoxin was increased. Epithelial cells showed enhanced expression of inflammation-related activation markers, along with enhanced luminal factors-driven recruitment of dendritic cells and Th17-biased lymphocyte infiltration into the lamina propria.
  
  
  CONCLUSIONS
  HFD feeding, independently of obesity, accelerated disease onset of small intestinal inflammation in Crohn's disease-relevant mouse model through mechanisms that involve increased intestinal permeability and altered luminal factors, leading to enhanced dendritic cell recruitment and promoted Th17 immune responses.
authors: Chair of Nutrition and Immunology, Technische Universität München, Freising-Weihenstephan, Germany ; Biofunctionality Unit, ZIEL - Research Center for Nutrition and Food Sciences, Technische Universität München, Freising-Weihenstephan, Germany.
authors: Lisa
authors: L
authors: Gruber
authors: Sigrid
authors: S
authors: Kisling
authors: Pia
authors: P
authors: Lichti
authors: François-Pierre
authors: FP
authors: Martin
authors: Stephanie
authors: S
authors: May
authors: Martin
authors: M
authors: Klingenspor
authors: Martina
authors: M
authors: Lichtenegger
authors: Michael
authors: M
authors: Rychlik
authors: Dirk
authors: D
authors: Haller
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D016764:Cell Polarity; D003424:Crohn Disease / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D003713:Dendritic Cells / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004731:Endotoxins / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D007079:Ileitis / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D007082:Ileum / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000276:immunology / Q000473:pathology; D062793:Occludin / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D004731:Endotoxins; D062793:Occludin; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose
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