The aromatic amino acid tryptophan stimulates skeletal muscle IGF1/p70s6k/mTor signaling in vivo and the expression of myogenic genes in vitro.
The aromatic amino acid tryptophan stimulates skeletal muscle IGF1/p70s6k/mTor signaling in vivo and the expression of myogenic genes in vitro.
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DOI：
10.1016/j.nut.2015.02.011
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Hamrick MW
中科院分区：
文献类型：
--
作者：
Dukes A;Davis C;El Refaey M;Upadhyay S;Mork S;Arounleut P;Johnson MH;Hill WD;Isales CM;Hamrick MW
营养在维持肌肉和骨量方面起着关键作用，饮食中蛋白质的缺乏尤其与肌肉和骨组织的分解代谢有关。一种将蛋白质缺乏与肌肉质量减少联系起来的机制被认为是缺乏在肌肉代谢中起作用的特定氨基酸。我们检验了必需氨基酸色氨酸及其代谢物犬尿氨酸可能直接影响蛋白质缺乏情况下肌肉代谢的假设。成年小鼠（12个月）分别饲喂正常饲粮（蛋白质含量18%）和低蛋白质饲粮（8%），并在饲粮中添加增加浓度（50、100和200 μ m）的犬尿氨酸（Kyn）或色氨酸（色氨酸；1.5 mM）。肌祖细胞也被Trp和Kyn体外处理，以确定它们对细胞增殖和肌分化标志物表达的影响。结果表明，低蛋白饮食组的小鼠体重均低于正常蛋白质饮食组（18%）。DXA测量的瘦质量在高犬尿氨酸饮食的小鼠中最低，而在补充色氨酸的小鼠中瘦质量百分比最高，而在接受色氨酸的小鼠中体脂百分比最低。ELISA检测显示，添加色氨酸后，骨骼肌IGF-1、瘦素和肌肉生长抑制素拮抗剂卵泡抑素显著增加。对肌肉样本进行的mRNA微阵列和基因通路分析表明，添加Kyn和Trp的小鼠肌肉中mTor/eif4/p70s6k通路分子显著上调。在体外，两种氨基酸都不影响肌祖细胞的增殖，但色氨酸增加了肌生成标志物MyoD、肌原蛋白和肌球蛋白重链的表达。总之，这些发现表明，膳食氨基酸可以直接影响骨骼肌的分子信号传导，进一步表明，特定氨基酸的饮食操纵可能会减轻膳食蛋白质缺乏导致的肌肉损失。
Nutrition plays a key role in the maintenance of muscle and bone mass, and dietary protein deficiency has in particular been associated with catabolism of both muscle and bone tissue. One mechanism thought to link protein deficiency with loss of muscle mass is deficiency in specific amino acids that play a role in muscle metabolism. We tested the hypothesis that the essential amino acid tryptophan, and its metabolite kynurenine, might directly impact muscle metabolism in the setting of protein deficiency. Adult mice (12 mo) were fed a normal diet (18% protein), as well as diets with low protein (8%) supplemented with increasing concentrations (50, 100, and 200 uM) of kynurenine (Kyn; or with tryptophan (Trp; 1.5 mM). Myoprogenitor cells were also treated with Trp and Kyn in vitro to determine their effects on cell proliferation and expression of myogenic differentiation markers. Results indicate that all mice on the low protein diets weighed less than the group fed normal protein (18%). Lean mass measured by DXA was lowest in mice on the high kynurenine diet, whereas percent lean mass was highest in mice receiving tryptophan supplementation and percent body fat was lowest in mice receiving tryptophan. ELISA assays showed significant increases in skeletal muscle IGF-1, leptin, and the myostatin antagonist follistatin with tryptophan supplementation. mRNA microarray and gene pathway analysis performed on muscle samples demonstrate that mTor/eif4/p70s6k pathway molecules are significantly up-regulated in muscles from mice on Kyn and Trp supplementation. In vitro, neither amino acid affected proliferation of myoprogenitors, but tryptophan increased the expression of the myogenic markers MyoD, myogenin, and myosin heavy chain. Together, these findings suggest that dietary amino acids can directly impact molecular signaling in skeletal muscle, further indicating that dietary manipulation with specific amino acids could potentially attenuate muscle loss with dietary protein deficiency.
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激活素A-乳腺抑制素系统对衰老的骨骼和肌肉祖细胞的影响。
影响因子：
3.9
作者：
Bowser, Matthew;Herberg, Samuel;Arounleut, Phonepasong;Shi, Xingming;Fulzele, Sadanand;Hill, William D.;Isales, Carlos M.;Hamrick, Mark W.
通讯作者：
Hamrick, Mark W.
DOI：
10.1177/0884533613507607
发表时间：
2013-12
期刊：
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition
影响因子：
--
作者：
Beasley JM;Shikany JM;Thomson CA
通讯作者：
Thomson CA
影响因子：
6.7
作者：
Narici, Marco V.;Maffulli, Nicola
通讯作者：
Maffulli, Nicola
影响因子：
4.1
作者：
Hamrick, MW;Pennington, C;Isales, C
通讯作者：
Isales, C
影响因子：
3.7
作者：
El Refaey M;Zhong Q;Hill WD;Shi XM;Hamrick MW;Bailey L;Johnson M;Xu J;Bollag WB;Chutkan N;Isales CM
通讯作者：
Isales CM