Document Detail


Impaired nutrient signaling and body weight control in a Na+ neutral amino acid cotransporter (Slc6a19)-deficient mouse.
MedLine Citation:
PMID:  21636576     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Amino acid uptake in the intestine and kidney is mediated by a variety of amino acid transporters. To understand the role of epithelial neutral amino acid uptake in whole body homeostasis, we analyzed mice lacking the apical broad-spectrum neutral (0) amino acid transporter B(0)AT1 (Slc6a19). A general neutral aminoaciduria was observed similar to human Hartnup disorder which is caused by mutations in SLC6A19. Na(+)-dependent uptake of neutral amino acids into the intestine and renal brush-border membrane vesicles was abolished. No compensatory increase of peptide transport or other neutral amino acid transporters was detected. Mice lacking B(0)AT1 showed a reduced body weight. When adapted to a standard 20% protein diet, B(0)AT1-deficient mice lost body weight rapidly on diets containing 6 or 40% protein. Secretion of insulin in response to food ingestion after fasting was blunted. In the intestine, amino acid signaling to the mammalian target of rapamycin (mTOR) pathway was reduced, whereas the GCN2/ATF4 stress response pathway was activated, indicating amino acid deprivation in epithelial cells. The results demonstrate that epithelial amino acid uptake is essential for optimal growth and body weight regulation.
Authors:
Angelika Bröer; Torsten Juelich; Jessica M Vanslambrouck; Nadine Tietze; Peter S Solomon; Jeff Holst; Charles G Bailey; John E J Rasko; Stefan Bröer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-02
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-25     Completed Date:  2011-09-28     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  26638-51     Citation Subset:  IM    
Affiliation:
Research School of Biology, Australian National University, Canberra, Australian Capital Territory 0200, Australia. Stefan.broer@anu.edu.au
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MeSH Terms
Descriptor/Qualifier:
Activating Transcription Factor 4 / genetics,  metabolism
Amino Acid Transport Systems, Neutral / genetics,  metabolism*
Animals
Body Weight / physiology*
Dietary Proteins
Eating / physiology*
Epithelial Cells / metabolism*
Hartnup Disease / genetics,  metabolism
Humans
Insulin / genetics,  secretion
Mice
Mice, Mutant Strains
Mutation
Protein-Serine-Threonine Kinases / genetics,  metabolism
Signal Transduction / physiology*
TOR Serine-Threonine Kinases / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Amino Acid Transport Systems, Neutral; 0/Atf4 protein, mouse; 0/Dietary Proteins; 0/Insulin; 0/SLC6A19 protein, mouse; 145891-90-3/Activating Transcription Factor 4; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.1.1/mTOR protein, mouse; EC 2.7.11.1/Eif2ak4 protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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