title: High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids.
abstract: OBJECTIVE
  To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism.
  
  
  METHODS
  Male C57Bl/6J mice were fed on a high-fat (n = 26) or low-fat diet (n = 24) for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile acids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF).
  
  
  RESULTS
  Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat, P = 0.03) and colon (0.335 for control vs 0.433 for high-fat, P = 0.01), but not in duodenum or ileum. The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P < 0.001). The proportion of ursodeoxycholic acid (UDCA) in all bile acids was decreased (1.4% ± 0.1% in high-fat vs 2.8% ± 0.3% in controls, P < 0.01) and correlated inversely with intestinal permeability (r = -0.72, P = 0.01). High-fat feeding also increased jejunal FXR expression, as well as TNF expression along the intestine, especially in the colon.
  
  
  CONCLUSIONS
  High-fat-feeding increased intestinal permeability, perhaps by a mechanism related to bile acid metabolism, namely a decreased proportion of fecal UDCA and increased FXR expression.
authors.affiliation: Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki 00280, Finland. lotta.stenman@helsinki.fi
authors.forename: Lotta K
authors.initials: LK
authors.lastname: Stenman
authors.forename: Reetta
authors.initials: R
authors.lastname: Holma
authors.forename: Riitta
authors.initials: R
authors.lastname: Korpela
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry / Q000378:metabolism*; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat / Q000009:adverse effects*; D005243:Feces / Q000737:chemistry*; D007422:Intestines / Q000033:anatomy & histology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability; D011897:Random Allocation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000737:chemistry / Q000378:metabolism; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D018160:Receptors, Cytoplasmic and Nuclear; D014409:Tumor Necrosis Factor-alpha; D014580:Ursodeoxycholic Acid; D000099150:Receptor, Farnesoid X-Activated