title: Role of the mTOR complex 1 pathway in the in vivo maintenance of the intestinal mucosa by oral intake of amino acids.
abstract: OBJECTIVE
  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.affiliation: Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakamura
authors.forename: Kenta
authors.initials: K
authors.lastname: Hara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hisafumi
authors.initials: H
authors.lastname: Yasuda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Moriyama
authors.forename: Midori
authors.initials: M
authors.lastname: Hirai
authors.forename: Masao
authors.initials: M
authors.lastname: Nagata
authors.forename: Koichi
authors.initials: K
authors.lastname: Yokono
mesh_terms: D000284:Administration, Oral; D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D001284:Atrophy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D015151:Immunoblotting; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D008810:Mice, Inbred C57BL; D046912:Multiprotein Complexes; D010766:Phosphorylation / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
chemical_list: D000596:Amino Acids; D046912:Multiprotein Complexes; D011506:Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases