Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn's disease

• Published in: Gut Vol. 61; no. 1; pp. 78 - 85
• Main Authors: Peyrin-Biroulet, Laurent, Gonzalez, Florent, Dubuquoy, Laurent, Rousseaux, Christel, Dubuquoy, Caroline, Decourcelle, Cécilia, Saudemont, Alain, Tachon, Mickael, Béclin, Elodie, Odou, Marie-Françoise, Neut, Christel, Colombel, Jean-Frédéric, Desreumaux, Pierre
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and British Society of Gastroenterology 01.01.2012; BMJ Publishing Group; BMJ Publishing Group LTD; BMJ Group
• Series: Original article
• Subjects: 6-mercaptopurine; 6-trinitrobenzene sulfonic acid; Abdominal Fat - metabolism; Abdominal Fat - microbiology; acute hepatitis; Adipocytes; Adult; alcoholic liver disease; Animals; anti-bacterial mucosal immunity; anti-bacterial peptide; antibacterial peptide; antibiotic therapy; antibiotics: clinical trials; azathioprine; bacteraemia; Bacteria; bacterial adherence; bacterial infection; bacterial overgrowth; bacterial pathogenesis; Bacterial Translocation; Biological and medical sciences; Biopsy; Biosynthesis; Body mass index; C Reactive protein; C-Reactive Protein - metabolism; cell biology; Cell Line; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - microbiology; Crohn Disease - metabolism; Crohn Disease - microbiology; Crohn's disease; Crohns disease; Cytokines; Escherichia coli; Escherichia coli - metabolism; Escherichia coli - physiology; Female; gastric neoplasia; Gastroenterology. Liver. Pancreas. Abdomen; genetic polymorphisms; Genotype & phenotype; Gram-negative bacteria; gut inflammation; Helicobacter pylori; Humans; IBD; IBD basic research; IBD clinical; IBD models; Ileitis - metabolism; Ileitis - microbiology; Inflammation; Inflammatory Bowel Disease; Interleukin-6 - metabolism; Lipopolysaccharides - metabolism; Lymph Nodes - microbiology; Lymphatic system; Male; Medical sciences; mesenteric fat; Mesentery - metabolism; Mesentery - microbiology; Mice; mucosal immunology; non-alcoholic steatohepatitis; non-ulcer dyspepsia; Other diseases. Semiology; Prospective Studies; Proteins; Rodents; small intestine; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Streptococcus infections; Studies; Surgery; thiopurine methyltransferase; TNF-alpha; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; ulcerative colitis; Infection; Translocation; Crohn disease; Gastroenterology; Bacteriosis; Fat; Digestive diseases; Intestinal disease; Mesentery; C reactive protein; Inflammatory disease
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gutjnl-2011-300370

ObjectiveMesenteric 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.DesignCRP 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.ResultsCRP 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.ConclusionMesenteric 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.