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Open AccessArticle

Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy

1
First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 5011194, Japan
2
Department of Hematology, Matsunami General Hospital, Gifu 5016062, Japan
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(4), 978; https://doi.org/10.3390/nu12040978
Received: 12 February 2020 / Revised: 25 March 2020 / Accepted: 30 March 2020 / Published: 1 April 2020
(This article belongs to the Section Nutrition and Metabolism)
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. View Full-Text
Keywords: tryptophan; sarcopenia; cancer; indoleamine 2,3-dioxygenase; glycolysis tryptophan; sarcopenia; cancer; indoleamine 2,3-dioxygenase; glycolysis
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Ninomiya, S.; Nakamura, N.; Nakamura, H.; Mizutani, T.; Kaneda, Y.; Yamaguchi, K.; Matsumoto, T.; Kitagawa, J.; Kanemura, N.; Shiraki, M.; Hara, T.; Shimizu, M.; Tsurumi, H. Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy. Nutrients 2020, 12, 978.

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