title: Butyrate and glucose metabolism by colonocytes in experimental colitis in mice.
abstract: OBJECTIVE
  Impaired colonocyte metabolism of butyrate has been implicated in the aetiopathogenesis of ulcerative colitis. Colonocyte butyrate metabolism was investigated in experimental colitis in mice.
  
  
  METHODS
  Colitis was induced in Swiss outbred white mice by oral administration of 4% dextran sulphate sodium (DSS). Colonocytes isolated from colitic and normal control mice were incubated with [(14)C]butyrate or glucose, and production of (14)CO(2), as well as of intermediate metabolites (acetoacetate, beta-hydroxybutyrate and lactate), was measured. The effect of different substrate concentrations on oxidation was also examined.
  
  
  RESULTS
  Butyrate oxidation (micromol/h per mg protein; mean (SEM)) was significantly reduced in DSS colitis, values on day 7 of DSS administration being 0.177 (0.007) compared with 0.406 (0.035) for control animals (p<0.001). Glucose oxidation (micromol/h per mg protein; mean (SEM)) on day 7 of DSS administration was significantly higher than in controls (0.06 (0.006) v 0.027 (0.004), p<0.001). Production of beta-hydroxybutyrate was decreased and production of lactate increased in DSS colitis compared with controls. Increasing butyrate concentration from 10 to 80 mM enhanced oxidation in DSS colitis (0.036 (0.002) to 0.285 (0.040), p<0.001), although it continued to remain lower than in controls. Surface and crypt epithelial cells showed similar ratios of butyrate to glucose oxidation. When 1 mM DSS was added to normal colonocytes in vitro, it did not alter butyrate oxidation. The initial histological lesion of DSS administration was very patchy and involved crypt cells. Abnormal butyrate oxidation became apparent only after six days of DSS administration, at which time histological abnormalities were more widespread.
  
  
  CONCLUSIONS
  Colonocyte metabolism of butyrate, but not of glucose, is impaired in DSS colitis, and may be important in pathophysiology. Histological abnormalities preceded measurable defects in butyrate oxidation.
authors.affiliation: The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College Hospital, Vellore 632004, India.
authors.forename: M S
authors.initials: MS
authors.lastname: Ahmad
authors.forename: S
authors.initials: S
authors.lastname: Krishnan
authors.forename: B S
authors.initials: BS
authors.lastname: Ramakrishna
authors.forename: M
authors.initials: M
authors.lastname: Mathan
authors.forename: A B
authors.initials: AB
authors.lastname: Pulimood
authors.forename: S N
authors.initials: SN
authors.lastname: Murthy
mesh_terms: D000818:Animals; D002087:Butyrates / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D016264:Dextran Sulfate; D005947:Glucose / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D010084:Oxidation-Reduction
chemical_list: D002087:Butyrates; D019344:Lactic Acid; D016264:Dextran Sulfate; D005947:Glucose