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Role of the mTOR complex 1 pathway in the in vivo maintenance of the intestinal mucosa by oral intake of amino acids
Author(s) -
Nakamura Akira,
Hara Kenta,
Yamamoto Kazuhiro,
Yasuda Hisafumi,
Moriyama Hiroaki,
Hirai Midori,
Nagata Masao,
Yokono Koichi
Publication year - 2012
Publication title -
geriatrics and gerontology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 57
eISSN - 1447-0594
pISSN - 1444-1586
DOI - 10.1111/j.1447-0594.2011.00729.x
Subject(s) - mtorc1 , pi3k/akt/mtor pathway , amino acid , intestinal mucosa , ribosomal protein s6 , phosphorylation , atrophy , endocrinology , medicine , in vivo , p70 s6 kinase 1 , biochemistry , biology , signal transduction , microbiology and biotechnology
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. Geriatr Gerontol Int 2012; 12: 131–139.