Metabolic alterations by indoxyl sulfate in skeletal muscle induce uremic sarcopenia in chronic kidney disease.
Metabolic alterations by indoxyl sulfate in skeletal muscle induce uremic sarcopenia in chronic kidney disease.
复制标题
硫酸吲哚酚引起的骨骼肌代谢改变可诱发慢性肾脏病患者的尿毒症肌少症。
DOI：
10.1038/srep36618
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发表时间：
2016-11-10
影响因子：
4.6
通讯作者：
Ito S
中科院分区：
文献类型：
--
作者：
Sato E;Mori T;Mishima E;Suzuki A;Sugawara S;Kurasawa N;Saigusa D;Miura D;Morikawa-Ichinose T;Saito R;Oba-Yabana I;Oe Y;Kisu K;Naganuma E;Koizumi K;Mokudai T;Niwano Y;Kudo T;Suzuki C;Takahashi N;Sato H;Abe T;Niwa T;Ito S
肌肉减少症与慢性肾脏病（CKD）的发病率和死亡率增加相关。慢性肾脏病（CKD）被定义为尿毒症性肌肉减少症，其骨骼肌丢失的发病机制尚不清楚。我们发现尿毒症性肌肉减少症的病理机制是由尿毒症毒素硫酸吲哚酚引起的代谢改变。成像质谱显示硫酸吲哚酚在CKD小鼠模型的肌肉组织中积累。综合代谢组学研究表明，硫酸吲哚酚通过核因子（红细胞-2相关因子）-2诱导代谢改变，如糖酵解上调，包括磷酸戊糖途径加速作为抗氧化应激反应。过度抗氧化反应的代谢流改变导致TCA循环下调，并影响肌细胞线粒体功能障碍和ATP缺乏。在临床研究中，观察到CKD患者的血浆硫酸吲哚酚与骨骼肌质量之间存在显著的负相关性。我们的研究结果表明，硫酸吲哚酚是一个致病因素，肌减少症在CKD。
Sarcopenia is associated with increased morbidity and mortality in chronic kidney disease (CKD). Pathogenic mechanism of skeletal muscle loss in CKD, which is defined as uremic sarcopenia, remains unclear. We found that causative pathological mechanism of uremic sarcopenia is metabolic alterations by uremic toxin indoxyl sulfate. Imaging mass spectrometry revealed indoxyl sulfate accumulated in muscle tissue of a mouse model of CKD. Comprehensive metabolomics revealed that indoxyl sulfate induces metabolic alterations such as upregulation of glycolysis, including pentose phosphate pathway acceleration as antioxidative stress response, via nuclear factor (erythroid-2-related factor)-2. The altered metabolic flow to excess antioxidative response resulted in downregulation of TCA cycle and its effected mitochondrial dysfunction and ATP shortage in muscle cells. In clinical research, a significant inverse association between plasma indoxyl sulfate and skeletal muscle mass in CKD patients was observed. Our results indicate that indoxyl sulfate is a pathogenic factor for sarcopenia in CKD.
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DOI：
10.1067/mlc.2001.113504
发表时间：
2001-04-01
期刊：
JOURNAL OF LABORATORY AND CLINICAL MEDICINE
影响因子：
--
作者：
Morley, JE;Baumgartner, RN;Nair, KS
通讯作者：
Nair, KS
影响因子：
4.2
作者：
Liabeuf S;Drüeke TB;Massy ZA
通讯作者：
Massy ZA
影响因子：
--
作者：
Adelibieke, Yelixiati;Yisireyili, Maimaiti;Niwa, Toshimitsu
通讯作者：
Niwa, Toshimitsu
影响因子：
19.6
作者：
BERGSTROM, J;FURST, P;LINDHOLM, B
通讯作者：
LINDHOLM, B
影响因子：
3
作者：
Cheung, Wai W.;Paik, Kyung Hoon;Mak, Robert H.
通讯作者：
Mak, Robert H.