Document Detail


Role of the mTOR complex 1 pathway in the in vivo maintenance of the intestinal mucosa by oral intake of amino acids.
MedLine Citation:
PMID:  21794051     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: Oral intake of nutrients is often compromised in elderly, multimorbid patients, but parenteral nutrition causes intestinal atrophy and impairs intestinal function. To uncover the molecular mechanisms by which amino acids are involved in intestinal atrophy and recovery, we studied whether the rapamycin-sensitive mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) pathway is involved in this process.
METHODS: C57BL/6N mice were fed a glucose solution alone, glucose solution with amino acids or normal chow diet for various lengths of time. Intestinal sections were prepared from these mice and the villus height and villus density were quantified. As a readout for the mTORC1 pathway, the phosphorylation of the ribosomal S6 protein (S6) was analyzed by immunostaining and immunoblotting. To confirm the role of the mTORC1 pathway, the inhibitory effect of a specific mTOR inhibitor, rapamycin, was examined.
RESULTS: Inducing fasting in mice fed only glucose caused time-dependent intestinal mucosal atrophy, whereas supplementation with amino acids protected the intestinal mucosa from atrophy. Phosphorylation of S6 decreased in the intestinal mucosa of mice fed only glucose, whereas supplementation with amino acids increased S6 phosphorylation. Importantly, intraperitoneal injection of rapamycin attenuated the protective effect of amino acids on the intestinal mucosa in a pattern consistent with the decrease of S6 phosphorylation.
CONCLUSIONS: These results indicate that the mTORC1 pathway plays a crucial role in the in vivo maintenance of the intestinal mucosa by the oral intake of amino acids.
Authors:
Akira Nakamura; Kenta Hara; Kazuhiro Yamamoto; Hisafumi Yasuda; Hiroaki Moriyama; Midori Hirai; Masao Nagata; Koichi Yokono
Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2011-07-27
Journal Detail:
Title:  Geriatrics & gerontology international     Volume:  12     ISSN:  1447-0594     ISO Abbreviation:  Geriatr Gerontol Int     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-22     Completed Date:  2012-05-22     Revised Date:  2013-09-30    
Medline Journal Info:
Nlm Unique ID:  101135738     Medline TA:  Geriatr Gerontol Int     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  131-9     Citation Subset:  IM    
Copyright Information:
© 2011 Japan Geriatrics Society.
Affiliation:
Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Amino Acids / administration & dosage*
Animals
Atrophy / metabolism,  pathology,  prevention & control
Disease Models, Animal
Immunoblotting
Intestinal Mucosa / drug effects,  metabolism*,  pathology
Male
Mice
Mice, Inbred C57BL
Phosphorylation / drug effects
Proteins / metabolism*
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Proteins; 0/mechanistic target of rapamycin complex 1

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


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