First Department of Internal Medicine, Gifu University Graduate School of Medicine, Gifu 5011194, Japan.
Department of Hematology, Matsunami General Hospital, Gifu 5016062, Japan.
Nutrients. 2020 Apr 1;12(4):978. doi: 10.3390/nu12040978.
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.
肌肉减少症是一些癌症患者预后不良的一个因素，但恶性肿瘤导致骨骼肌萎缩的机制知之甚少。色氨酸代谢由吲哚胺 2,3-双加氧酶介导，是与癌症进展相关的最重要的氨基酸变化之一。本文证明了骨骼肌与低色氨酸水平之间的关系。弥漫性大 B 细胞淋巴瘤患者的骨骼肌体积与血清色氨酸水平呈正相关。低水平的色氨酸降低 C2C12 成肌细胞的增殖和分化。用色氨酸缺乏饮食喂养的 C57BL/6 小鼠的比目鱼肌中的纤维直径小于用标准饮食喂养的小鼠。代谢组学分析显示，色氨酸缺乏饮食下调了腓肠肌中的糖酵解作用，上调了与三羧酸循环相关的氨基酸浓度。改用标准饮食后，用色氨酸缺乏饮食喂养的小鼠的体重和肌纤维直径恢复。我们的数据表明色氨酸在调节骨骼肌质量方面起着关键作用。因此，色氨酸代谢途径可能是预防或治疗骨骼肌萎缩的有前途的靶点。
