title: Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn's disease.
abstract: OBJECTIVE
  Mesenteric fat hyperplasia is a hallmark of Crohn's disease (CD), and C reactive protein (CRP) is correlated with disease activity. The authors investigated whether mesenteric adipocytes may be a source of CRP in CD and whether inflammatory and bacterial triggers may stimulate its production by adipocytes.
  
  
  METHODS
  CRP expression in the mesenteric and subcutaneous fats of patients with CD and the correlation between CRP plasma concentrations and mesenteric messenger RNA (mRNA) levels were assessed. The impact of inflammatory and bacterial challenges on CRP synthesis was tested using an adipocyte cell line. Bacterial translocation to mesenteric fat was studied in experimental models of colitis and ileitis and in patients with CD.
  
  
  RESULTS
  CRP expression was increased in the mesenteric fat of patients with CD, with mRNA levels being 80 ± 40 (p<0.05) and 140 ± 65 (p=0.04) times higher than in the mesenteric fat of patients with ulcerative colitis and in the subcutaneous fat of the same CD subjects, respectively, and correlated with plasma levels. Escherichia coli (1230 ± 175-fold, p<0.01), lipopolysaccharide (26 ± 0.5-fold, p<0.01), tumour necrosis factor α (15 ± 0.3-fold, p<0.01) and interleukin-6 (10 ± 0.7-fold, p<0.05) increased CRP mRNA levels in adipocyte 3T3-L1 cells. Bacterial translocation to mesenteric fat occurred in 13% and 27% of healthy and CD subjects, respectively, and was increased in experimental colitis and ileitis. Human mesenteric adipocytes constitutively expressed mRNA for TLR2, TLR4, NOD1 and NOD2.
  
  
  CONCLUSIONS
  Mesenteric fat is an important source of CRP in CD. CRP production by mesenteric adipocytes may be triggered by local inflammation and bacterial translocation to mesenteric fat, providing a mechanism whereby mesenteric fat hyperplasia may contribute to inflammatory response in CD.
authors.affiliation: Universitè Lille Nord de France, Lille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.forename: Florent
authors.initials: F
authors.lastname: Gonzalez
authors.forename: Laurent
authors.initials: L
authors.lastname: Dubuquoy
authors.forename: Christel
authors.initials: C
authors.lastname: Rousseaux
authors.forename: Caroline
authors.initials: C
authors.lastname: Dubuquoy
authors.forename: Cécilia
authors.initials: C
authors.lastname: Decourcelle
authors.forename: Alain
authors.initials: A
authors.lastname: Saudemont
authors.forename: Mickael
authors.initials: M
authors.lastname: Tachon
authors.forename: Elodie
authors.initials: E
authors.lastname: Béclin
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Odou
authors.forename: Christel
authors.initials: C
authors.lastname: Neut
authors.forename: Jean-Frédéric
authors.initials: JF
authors.lastname: Colombel
authors.forename: Pierre
authors.initials: P
authors.lastname: Desreumaux
mesh_terms: D050153:Abdominal Fat / Q000378:metabolism* / Q000382:microbiology; D000328:Adult; D000818:Animals; D018988:Bacterial Translocation; D002097:C-Reactive Protein / Q000378:metabolism*; D002460:Cell Line; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000382:microbiology; D003424:Crohn Disease / Q000378:metabolism* / Q000382:microbiology; D004926:Escherichia coli / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D007079:Ileitis / Q000378:metabolism / Q000382:microbiology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008198:Lymph Nodes / Q000382:microbiology; D008297:Male; D008643:Mesentery / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein