title: Adiponectin deficiency protects mice from chemically induced colonic inflammation.
abstract: OBJECTIVE
  Adiponectin (APN) is an adipokine that regulates insulin sensitivity and is anti-inflammatory in atherosclerosis. The goal of this study was to investigate the role of APN in intestinal inflammation.
  
  
  METHODS
  APN knockout (KO) mice and their wild-type (WT) littermates received dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) to induce intestinal inflammation. Clinical and histologic scores and proliferation of epithelial cells were assessed. Cytokines and APN levels were measured. Expression of APN and heparin binding epidermal growth factor (HB-EGF) was analyzed by immunohistochemistry. Expression of APN and its receptors, HB-EGF, and basic fibroblast growth factor (bFGF) messenger RNA was assessed by reverse-transcription polymerase chain reaction. Association of serum APN with HB-EGF and bFGF was studied by coimmunoprecipitation.
  
  
  RESULTS
  APN KO mice are protected from chemically induced colitis; administration of APN restores inflammation. APN is expressed in the colon, luminal APN associates with colonic epithelial cells. In vitro, APN increases production of proinflammatory cytokines from colonic tissue. Expression of colonic APN overlaps with that of bFGF and HB-EGF, which play a protective role in colitis. Circulating APN binds to bFGF and HB-EGF, likely inhibiting their protective activity. Inhibition of EGF receptor signaling, which is required for biologic activity of HB-EGF, restores inflammation in APN KO mice.
  
  
  CONCLUSIONS
  APN deficiency is associated with protection from chemically induced colitis. APN exerts proinflammatory activities in the colon by inducing production of proinflammatory cytokines and inhibiting bioactivity of protective growth factors. Thus, in colitis, APN exerts an opposite role compared with atherosclerosis.
authors.affiliation: Department of Human Nutrition, University of Illinois at Chicago, 60612, USA.
authors.forename: Raja
authors.initials: R
authors.lastname: Fayad
authors.forename: Maria
authors.initials: M
authors.lastname: Pini
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sennello
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Cabay
authors.forename: Lawrence
authors.initials: L
authors.lastname: Chan
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Giamila
authors.initials: G
authors.lastname: Fantuzzi
mesh_terms: D052242:Adiponectin / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology; D000818:Animals; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016207:Cytokines; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate