Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice
Dose-dependent effects of leucine supplementation on preservation of muscle mass in cancer cachectic mice
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DOI：
10.3892/or.2011.1269
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发表时间：
2011-07-01
期刊：
影响因子：
4.2
通讯作者：
Van Norren, K.
中科院分区：
文献类型：
--
作者：
Peters, S. J.;Van Helvoort, A.;Van Norren, K.
以肌肉萎缩为特征的癌症恶病质与发病率和死亡率的增加有关。由于补充亮氨酸可以增加肌肉蛋白质合成，减少蛋白质分解，我们使用C26肿瘤恶病质小鼠模型来评估饮食补充亮氨酸对肌肉重量和肌肉蛋白质分解标志物(阿托金和MURF的信使核糖核酸)的影响。雄性CD2F1小鼠皮下接种肿瘤细胞(荷瘤小鼠；TB)或假注射(对照组；C)。分别饲喂标准日粮或添加亮氨酸[每千克饲料中添加亮氨酸1gr(TB1Leu)或8gr(TB8Leu)]，试验组和试验组分别饲喂8.7%Leu/g蛋白质、9.6%Leu/g蛋白质和14.6 Leu/g蛋白质。21d后测定体重、血浆氨基酸浓度、腓肠肌(Mg)、胫前肌(MTA)、趾长伸肌(MEDL)和比目鱼肌(Ms)的肿瘤大小和肌肉质量。在荷瘤(TB)小鼠中，身体和骨骼肌块减少，MEDL中阿托品和Murf mRNA的水平增加。补充亮氨酸可抑制肌肉质量的下降，且呈剂量依赖关系：相对于TB，Tb8Leu组镁的质量为+23%，MTA组为+22%(p<；0.05)。然而，补充亮氨酸并没有改变阿托金和Murf的mRNA水平。TB患者血浆总氨基酸浓度升高，尤其是牛磺酸、赖氨酸、精氨酸和丙氨酸(p<；0.05)。补充亮氨酸可以减轻血浆总氨基酸浓度的升高(p<；0.05)。不管肌肉蛋白质分解标志物的变化如何，补充亮氨酸减少了荷瘤恶病质小鼠的肌肉损耗，并减弱了血浆氨基酸的变化。
Cancer cachexia, which is characterized by muscle wasting, is associated with increased morbidity and mortality. Because muscle protein synthesis may be increased and protein breakdown reduced by leucine supplementation, we used the C26 tumor-bearing cachectic mouse model to assess the effects of dietary supplementation with leucine on muscle weight and the markers of muscle protein breakdown (mRNA of atrogin and murf). Male CD2F1 mice were subcutaneously inoculated with tumor cells (tumor-bearing mice; TB) or were sham injected (control; C). They were fed standard diets or diets supplemented with leucine [1 gr (TB1Leu) or 8 gr (TB8Leu) supplemented leucine per kg feed]; TB and C received 8.7% Leu/g protein, TB1Leu received 9.6% Leu/g protein and TB8Leu received 14.6 Leu/g protein. After 21 days, the following were determined: body weights, plasma amino-acid concentrations, tumor size and muscle mass of the gastrocnemius (mG), tibialis anterior (mTA), extensor digitorum longus (mEDL) and soleus (mS) muscles. In tumor-bearing (TB) mice, carcass and skeletal muscle masses decreased, and levels of atrogin and murf mRNA in the mEDL increased. Muscle-mass loss was counteracted dose-dependently by leucine supplementation: relative to TB, the mass of the mG was +23% in TB8Leu, and +22% in mTA (p < 0.05). However, leucine supplementation did not change atrogin and murf mRNA levels. Total plasma amino acid concentrations increased in TB, especially for taurine, lysine, arginine and alanine (p < 0.05). Leucine supplementation attenuated the increase in total plasma amino-acid concentrations (p < 0.05). Irrespective of changes in muscle protein breakdown markers, leucine supplementation reduced muscle wasting in tumor-bearing cachectic mice and attenuated changes in plasma amino acids.