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Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy

Sarcopenia is a poor prognosis factor in some cancer patients, but little is known about the mechanisms by which malignant tumors cause skeletal muscle atrophy. Tryptophan metabolism mediated by indoleamine 2,3-dioxygenase is one of the most important amino acid changes associated with cancer progre...

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Autores principales: Ninomiya, Soranobu, Nakamura, Nobuhiko, Nakamura, Hiroshi, Mizutani, Taku, Kaneda, Yuto, Yamaguchi, Kimihiro, Matsumoto, Takuro, Kitagawa, Junichi, Kanemura, Nobuhiro, Shiraki, Makoto, Hara, Takeshi, Shimizu, Masahito, Tsurumi, Hisashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230402/
https://www.ncbi.nlm.nih.gov/pubmed/32244785
http://dx.doi.org/10.3390/nu12040978
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author Ninomiya, Soranobu
Nakamura, Nobuhiko
Nakamura, Hiroshi
Mizutani, Taku
Kaneda, Yuto
Yamaguchi, Kimihiro
Matsumoto, Takuro
Kitagawa, Junichi
Kanemura, Nobuhiro
Shiraki, Makoto
Hara, Takeshi
Shimizu, Masahito
Tsurumi, Hisashi
author_facet Ninomiya, Soranobu
Nakamura, Nobuhiko
Nakamura, Hiroshi
Mizutani, Taku
Kaneda, Yuto
Yamaguchi, Kimihiro
Matsumoto, Takuro
Kitagawa, Junichi
Kanemura, Nobuhiro
Shiraki, Makoto
Hara, Takeshi
Shimizu, Masahito
Tsurumi, Hisashi
author_sort Ninomiya, Soranobu
collection PubMed
description Sarcopenia is a poor prognosis factor in some cancer patients, but little is known about the mechanisms by which malignant tumors cause skeletal muscle atrophy. Tryptophan metabolism mediated by indoleamine 2,3-dioxygenase is one of the most important amino acid changes associated with cancer progression. Herein, we demonstrate the relationship between skeletal muscles and low levels of tryptophan. A positive correlation was observed between the volume of skeletal muscles and serum tryptophan levels in patients with diffuse large B-cell lymphoma. Low levels of tryptophan reduced C2C12 myoblast cell proliferation and differentiation. Fiber diameters in the tibialis anterior of C57BL/6 mice fed a tryptophan-deficient diet were smaller than those in mice fed a standard diet. Metabolomics analysis revealed that tryptophan-deficient diet downregulated glycolysis in the gastrocnemius and upregulated the concentrations of amino acids associated with the tricarboxylic acid cycle. The weights and muscle fiber diameters of mice fed the tryptophan-deficient diet recovered after switching to the standard diet. Our data showed a critical role for tryptophan in regulating skeletal muscle mass. Thus, the tryptophan metabolism pathway may be a promising target for preventing or treating skeletal muscle atrophies.
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spelling pubmed-72304022020-05-22 Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy Ninomiya, Soranobu Nakamura, Nobuhiko Nakamura, Hiroshi Mizutani, Taku Kaneda, Yuto Yamaguchi, Kimihiro Matsumoto, Takuro Kitagawa, Junichi Kanemura, Nobuhiro Shiraki, Makoto Hara, Takeshi Shimizu, Masahito Tsurumi, Hisashi Nutrients Article Sarcopenia is a poor prognosis factor in some cancer patients, but little is known about the mechanisms by which malignant tumors cause skeletal muscle atrophy. Tryptophan metabolism mediated by indoleamine 2,3-dioxygenase is one of the most important amino acid changes associated with cancer progression. Herein, we demonstrate the relationship between skeletal muscles and low levels of tryptophan. A positive correlation was observed between the volume of skeletal muscles and serum tryptophan levels in patients with diffuse large B-cell lymphoma. Low levels of tryptophan reduced C2C12 myoblast cell proliferation and differentiation. Fiber diameters in the tibialis anterior of C57BL/6 mice fed a tryptophan-deficient diet were smaller than those in mice fed a standard diet. Metabolomics analysis revealed that tryptophan-deficient diet downregulated glycolysis in the gastrocnemius and upregulated the concentrations of amino acids associated with the tricarboxylic acid cycle. The weights and muscle fiber diameters of mice fed the tryptophan-deficient diet recovered after switching to the standard diet. Our data showed a critical role for tryptophan in regulating skeletal muscle mass. Thus, the tryptophan metabolism pathway may be a promising target for preventing or treating skeletal muscle atrophies. MDPI 2020-04-01 /pmc/articles/PMC7230402/ /pubmed/32244785 http://dx.doi.org/10.3390/nu12040978 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ninomiya, Soranobu
Nakamura, Nobuhiko
Nakamura, Hiroshi
Mizutani, Taku
Kaneda, Yuto
Yamaguchi, Kimihiro
Matsumoto, Takuro
Kitagawa, Junichi
Kanemura, Nobuhiro
Shiraki, Makoto
Hara, Takeshi
Shimizu, Masahito
Tsurumi, Hisashi
Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy
title Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy
title_full Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy
title_fullStr Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy
title_full_unstemmed Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy
title_short Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy
title_sort low levels of serum tryptophan underlie skeletal muscle atrophy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230402/
https://www.ncbi.nlm.nih.gov/pubmed/32244785
http://dx.doi.org/10.3390/nu12040978
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