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Defective intestinal amino acid absorption in Ace2 null mice.
MedLine Citation:
PMID:  22790597     Owner:  NLM     Status:  Publisher    
Mutations in the main intestinal and kidney luminal neutral amino acid transporter B(0)AT1 (Slc6a19) lead to Hartnup disorder, a condition that is characterized by neutral aminoaciduria and in some cases pellagra-like symptoms. These latter symptoms caused by low niacin are thought to result from defective intestinal absorption of its precursor L-tryptophan. Since angiotensin-converting enzyme 2 (Ace2) is necessary for intestinal B(0)AT1 expression, we tested the impact of intestinal B(0)AT1 absence in ace2 null mice. Their weight gain following weaning was decreased and Na(+)-dependent uptake of B(0)AT1 substrates measured in everted intestinal rings defective. Additionally, high affinity Na(+)-dependent transport of L-proline, presumably via SIT1 (Slc6a20), was absent, whereas glucose uptake via SGLT1 (Slc5a1) was not affected. Measurements of small intestine luminal amino acid content following gavage showed that more L-tryptophan than other B(0)AT1 substrates reach the ileum in wild-type mice, which is in line with its known lower apparent affinity. In ace2 null mice, the absorption defect was confirmed by a several fold increase of L-tryptophan and of other neutral amino acids reaching the ileum lumen. Furthermore, plasma and muscle levels of glycine and L-tryptophan were significantly decreased in ace2 null mice, with other neutral amino acids displaying a similar trend. A low protein / low niacin diet challenge led to differential changes in plasma amino acid levels in both wild-type and ace2 null mice, but only in ace2 null mice to a stop in weight gain. Despite the combination of low niacin with low protein diet, plasma niacin concentrations remained normal in ace2 null mice and no pellagra symptoms such as photosensitive skin rash or ataxia were observed. In summary, mice lacking Ace2-dependent intestinal amino acid transport display no total niacin deficiency nor clear pellagra symptoms, even under low protein and low niacin diet, despite gross amino acid homeostasis alterations.
Dustin Singer; Simone M R Camargo; Tamara Ramadan; Matthias Schäfer; Luca Mariotta; Brigitte Herzog; Katja Huggel; David Wolfer; Sabine Werner; Josef M Penninger; Francois Verrey
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-12
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  -     ISSN:  1522-1547     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1University of Zurich.
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