Spontaneous development of intestinal and colonic atrophy and inflammation in the carnitine-deficient jvs (OCTN2(-/-)) mice

Mol Genet Metab. 2007 Dec;92(4):315-24. doi: 10.1016/j.ymgme.2007.08.002. Epub 2007 Sep 19.


Carnitine is essential for transport of long-chain fatty acids into mitochondria for their subsequent beta-oxidation, but its role in the gastrointestinal tract has not been well described. Recently several genetic epidemiologic studies have shown strong association between mutations in carnitine transporter genes OCTN1 and OCTN2 and a propensity to develop Crohn's disease. This study aims to investigate role of carnitine and beta-oxidation in the GI tract. We have studied the gastrointestinal tract effects of carnitine deficiency in a mouse model with loss-of-function mutation in the OCTN2 carnitine transporter. juvenile visceral steatosis (OCTN2(-/-)) mouse spontaneously develops intestinal villous atrophy, breakdown and inflammation with intense lymphocytic and macrophage infiltration, leading to ulcer formation and gut perforation. There is increased apoptosis of jvs (OCTN2(-/-)) gut epithelial cells. We observed an up-regulation of heat shock factor-1 (HSF-1) and several heat shock proteins (HSPs) which are known to regulate OCTN2 gene expression. Intestinal and colonic epithelial cells in wild type mice showed high expression and activity of the enzymes of beta-oxidation pathway. These studies provide evidence of an obligatory role for carnitine in the maintenance of normal intestinal and colonic structure and morphology. Fatty acid oxidation, a metabolic pathway regulated by carnitine-dependent entry of long-chain fatty acids into mitochondrial matrix, is likely essential for normal gut function. Our studies suggest that carnitine supplementation, as a means of boosting fatty acid oxidation, may be therapeutically beneficial in patients with inflammation of the intestinal tract.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Transport Systems
  • Animals
  • Atrophy / etiology
  • Carnitine / deficiency*
  • Carnitine / metabolism
  • Colon / abnormalities
  • Crohn Disease / metabolism
  • Crohn Disease / physiopathology*
  • DNA-Binding Proteins / metabolism*
  • Disease Models, Animal
  • Fatty Acids / metabolism
  • Heat Shock Transcription Factors
  • Inflammation / etiology*
  • Intestines / abnormalities
  • Membrane Transport Proteins / genetics
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • Organic Cation Transport Proteins*
  • Transcription Factors / metabolism*


  • Amino Acid Transport Systems
  • DNA-Binding Proteins
  • Fatty Acids
  • Heat Shock Transcription Factors
  • Hsf1 protein, mouse
  • Membrane Transport Proteins
  • Organic Cation Transport Proteins
  • Transcription Factors
  • Carnitine