title: Gut barrier dysfunction in the Apc(Min/+) mouse model of colon cancer cachexia.
abstract: BACKGROUND
  The Apc(Min/+) mouse, an animal model of colorectal cancer and cachexia, has a heterologous mutation in the Apc tumor suppressor gene, predisposing the mouse to intestinal and colon tumor development. This mouse develops intestinal polyps by ~4 weeks of age, and loses body weight gradually between ~14 and ~20 weeks of age. The strengths of this cachexia model derive from several features that mimic human cancer, including a gradual increase in tumor burden, chronic inflammation, and anemia. Little is known about the role of gut barrier dysfunction and endotoxemia in the development of cancer cachexia. We sought to determine how gut permeability and resultant endotoxemia change with the progression of cachexia.
  
  
  METHODS
  Intestinal gut barrier integrity was assessed by permeability to FITC-dextran (MW(av)=4000kDa; FD4). Plasma glucose and triglycerides were measured by enzymatic assays, IL-6 by enzyme-linked immunosorbent assay, and endotoxin by the limulus amoebocyte assay. Body temperature was measured using a rectal probe.
  
  
  RESULTS
  Progression of cachexia was accompanied by development of gut barrier dysfunction (permeability to FD4), hypertrophy of mesenteric lymph nodes, and an increase in plasma endotoxin concentration. Changes in blood glucose and glucose tolerance, plasma IL-6, triglycerides, and body temperature were characteristic of endotoxemia.
  
  
  CONCLUSIONS
  We propose a role for gut barrier dysfunction (GBD) and subsequent endotoxemia in the development of inflammation and progression of cachexia in the Apc(Min/+) mouse.
authors.affiliation: Department of Exercise Science, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Puppa
authors.forename: James P
authors.initials: JP
authors.lastname: White
authors.forename: Shuichi
authors.initials: S
authors.lastname: Sato
authors.forename: Mark
authors.initials: M
authors.lastname: Cairns
authors.forename: John W
authors.initials: JW
authors.lastname: Baynes
authors.forename: James A
authors.initials: JA
authors.lastname: Carson
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000818:Animals; D002100:Cachexia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D003110:Colonic Neoplasms / Q000150:complications*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000209:etiology; D004731:Endotoxins / Q000097:blood; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology; D007035:Hypothermia / Q000209:etiology; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010539:Permeability; D047368:Tumor Burden
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D004731:Endotoxins; D015850:Interleukin-6