title: Effects of obesity on severity of colitis and cytokine expression in mouse mesenteric fat. Potential role of adiponectin receptor 1.
abstract: In inflammatory bowel disease (IBD), obesity is associated with worsening of the course of disease. Here, we examined the role of obesity in the development of colitis and studied mesenteric fat-epithelial cell interactions in patients with IBD. We combined the diet-induce obesity with the trinitrobenzene sulfonic acid (TNBS) colitis mouse model to create groups with obesity, colitis, and their combination. Changes in the mesenteric fat and intestine were assessed by histology, myeloperoxidase assay, and cytokine mRNA expression by real-time PCR. Medium from human mesenteric fat and cultured preadipocytes was obtained from obese patients and those with IBD. Histological analysis showed inflammatory cell infiltrate and increased histological damage in the intestine and mesenteric fat of obese mice with colitis compared with all other groups. Obesity also increased the expression of proinflammatory cytokines including IL-1β, TNF-α, monocyte chemoattractant protein 1, and keratinocyte-derived chemokine, while it decreased the TNBS-induced increases in IL-2 and IFN-γ in mesenteric adipose and intestinal tissues. Human mesenteric fat isolated from obese patients and those with and IBD demonstrated differential release of adipokines and growth factors compared with controls. Fat-conditioned media reduced adiponectin receptor 1 (AdipoR1) expression in human NCM460 colonic epithelial cells. AdipoR1 intracolonic silencing in mice exacerbated TNBS-induced colitis. In conclusion, obesity worsens the outcome of experimental colitis, and obesity- and IBD-associated changes in adipose tissue promote differential mediator release in mesenteric fat that modulates colonocyte responses and may affect the course of colitis. Our results also suggest an important role for AdipoR1 for the fat-intestinal axis in the regulation of inflammation during colitis.
authors.affiliation: Inflammatory Bowel Disease Center, and Neuroendocrine Assay Core, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California; Postgraduate Program: Molecular Medicine, University of Crete, Medical School, Crete, Greece.
authors.forename: Aristea
authors.initials: A
authors.lastname: Sideri
authors.affiliation: Inflammatory Bowel Disease Center, and Neuroendocrine Assay Core, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California;
authors.forename: Dimitris
authors.initials: D
authors.lastname: Stavrakis
authors.affiliation: Inflammatory Bowel Disease Center, and Neuroendocrine Assay Core, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California;
authors.forename: Collin
authors.initials: C
authors.lastname: Bowe
authors.affiliation: Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, California;
authors.forename: David Q
authors.initials: DQ
authors.lastname: Shih
authors.affiliation: Inflammatory Bowel and Immunobiology Research Institute, Cedars Sinai Medical Center, Los Angeles, California;
authors.forename: Phillip
authors.initials: P
authors.lastname: Fleshner
authors.affiliation: Inflammatory Bowel Diseases Center, Division of Gastroenterology, Hepatology and Nutrition, Wexner Medical Center, Ohio State University, Columbus, Ohio;
authors.forename: Violeta
authors.initials: V
authors.lastname: Arsenescu
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Wexner Medical Center, Ohio State University, Columbus, Ohio;
authors.forename: Razvan
authors.initials: R
authors.lastname: Arsenescu
authors.affiliation: Department of Pathology, The University of Chicago, Chicago, Illinois; Department of Medicine, The University of Chicago, Chicago, Illinois;
authors.forename: Jerrold R
authors.initials: JR
authors.lastname: Turner
authors.affiliation: Inflammatory Bowel Disease Center, and Neuroendocrine Assay Core, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California;
authors.forename: Charalabos
authors.initials: C
authors.lastname: Pothoulakis
authors.affiliation: Inflammatory Bowel Disease Center, and Neuroendocrine Assay Core, Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, California; ikaragiannidis@mednet.ucla.edu.
authors.forename: Iordanes
authors.initials: I
authors.lastname: Karagiannides
mesh_terms: D050153:Abdominal Fat / Q000276:immunology / Q000378:metabolism*; D052438:Adipocytes, White / Q000276:immunology / Q000378:metabolism*; D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017077:Culture Media, Conditioned / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000378:metabolism*; D012720:Severity of Illness Index; D015398:Signal Transduction; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
chemical_list: C475418:ADIPOR1 protein, human; D054392:Adipokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; D014302:Trinitrobenzenesulfonic Acid
keywords: adipokines; adipose tissue; colitis; obesity