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Inflammatory bowel disease
Original article
Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn's disease
  1. Laurent Peyrin-Biroulet1,2,3,4,
  2. Florent Gonzalez1,2,3,4,
  3. Laurent Dubuquoy1,2,3,4,
  4. Christel Rousseaux1,2,3,4,
  5. Caroline Dubuquoy1,2,3,4,
  6. Cécilia Decourcelle1,2,3,4,
  7. Alain Saudemont5,
  8. Mickael Tachon1,2,3,4,6,
  9. Elodie Béclin1,2,3,4,6,
  10. Marie-Françoise Odou1,2,3,4,6,
  11. Christel Neut1,2,3,4,6,
  12. Jean-Frédéric Colombel1,2,3,4,
  13. Pierre Desreumaux1,2,3,4
  1. 1Universitè Lille Nord de France, Lille, France
  2. 2Inserm U995, Lille, France
  3. 3UDSL, Lille, France
  4. 4Service des Maladies de l'Appareil Digestif et de la Nutrition, CHU Lille, Lille, France
  5. 5Service de Chirurgie Adultes Ouest, CHU Lille, Lille, France
  6. 6Laboratoire de Bactériologie Clinique, Faculté de Pharmacie de Lille, Lille, France
  1. Correspondence to Professor Pierre Desreumaux, Inserm U995, Faculté de Médecine Pôle Recherche, Amphi J-K, Bld du Pr Jules Leclercq, F-59045 Lille Cedex, France; pdesreumaux{at}hotmail.com

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.

Design 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.

Conclusion 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.

  • C Reactive protein
  • mesenteric fat
  • bacterial translocation
  • Crohn's disease
  • IBD basic research
  • 6-mercaptopurine
  • bacterial translocation
  • IBD
  • thiopurine methyltransferase
  • antibacterial peptide
  • IBD models
  • azathioprine
  • IBD clinical
  • 2,4,6-trinitrobenzene sulfonic acid
  • acute hepatitis
  • alcoholic liver disease
  • anti-bacterial mucosal immunity
  • gut inflammation
  • anti-bacterial peptide
  • antibiotic therapy
  • antibiotics: clinical trials
  • bacteraemia
  • bacterial overgrowth
  • bacterial translocation
  • bacterial infection
  • bacterial pathogenesis
  • bacterial adherence
  • crohn's disease
  • TNF-alpha
  • ulcerative colitis
  • small intestine
  • cell biology
  • inflammatory bowel disease
  • mucosal immunology
  • Helicobacter pylori
  • non-ulcer dyspepsia
  • genetic polymorphisms
  • gastric neoplasia
  • non-alcoholic steatohepatitis
  • gut inflammation
  • alcoholic liver disease
  • cytokines

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

https://doi.org/10.1136/gutjnl-2011-300370

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    Footnotes

    • See Commentary, p 3

    • Funding IRMAD/Astrazeneca, Institut Universitaire de France, Association François Aupetit.

    • Competing interests None.

    • Ethics approval Ethical guidelines in studies on humans were followed under the supervision of an investigator, and human samples were declared to Inserm according to French laws (articles L. 1243-3 and R. 1243-49, and the Code de la Santé Publique).

    • Provenance and peer review Not commissioned; externally peer reviewed.

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