Spontaneous development of intestinal and colonic atrophy and inflammation in the carnitine-deficient jvs (OCTN2(-/-)) mice
| Autor: | Puttur D. Prasad, Prem S. Shekhawat, Sonne R. Srinivas, Penny Roon, Michael J. Bennett, Dietrich Matern, Varghese George, Vadivel Ganapathy, Richard L. Boriack, Hongyan Xu |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Amino Acid Transport Systems Organic Cation Transport Proteins Colon Endocrinology Diabetes and Metabolism Perforation (oil well) Inflammation Biology Mitochondrion Biochemistry Article Mice Endocrinology Atrophy Crohn Disease Heat Shock Transcription Factors Internal medicine Heat shock protein Carnitine Genetics medicine Animals Molecular Biology Beta oxidation Gastrointestinal tract Fatty Acids Membrane Transport Proteins medicine.disease Mice Mutant Strains DNA-Binding Proteins Intestines Disease Models Animal Immunology Mutation medicine.symptom medicine.drug Transcription Factors |
| Zdroj: | Molecular genetics and metabolism. 92(4) |
| ISSN: | 1096-7192 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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