Wan Jin, Chen Daiwen, Yu Bing, Luo Yuheng, Mao Xiangbing, Zheng Ping, Yu Jie, Luo Junqiu, He Jun
Institute of Animal Nutrition, Sichuan Agricultural University , Chengdu, Wenjiang District, Sichuan, China .
J Med Food. 2017 Jan;20(1):93-101. doi: 10.1089/jmf.2016.3759. Epub 2016 Dec 23.
Skeletal muscle atrophy is a decrease in muscle mass that occurs when protein degradation exceeds protein synthesis. Leucine (Leu), an essential branched-chain amino acid in animal nutrition, regulates skeletal muscle protein metabolism. Two experiments were conducted to evaluate whether Leu could alleviate lipopolysaccharide (LPS)-induced skeletal muscle wasting by modulating skeletal muscle protein synthesis and degradation. A total of 24 rats were randomly allocated into three groups (n = 8): (1) non-challenged control; (2) LPS-challenged control; and (3) LPS +3.0% Leu. Rats were fed with control or Leu-supplemented (part of the casein was replaced with 3.0% Leu) diets throughout the trial and were injected intraperitoneally with sterile saline or LPS at days 6, 11, 16, and 21. On the morning of day 22, serum samples were collected and rats were then sacrificed for liver and muscle analysis. In vitro protein degradation, nuclear factor-κB (NF-κB) activity, and proteolytic enzyme activities of the muscles from immune-challenged rats were also measured. Our results showed that the LPS challenge resulted in not only enhanced serum interleukin-1 and liver C-reactive protein (CRP) concentrations but also decreased the average daily body weight gain and muscle fiber diameter. However, dietary Leu inclusion attenuated the increase in CRP level and the decrease in muscle fiber diameter. Importantly, the LPS challenge caused a significant elevation in the muscle proteolysis rate, but dietary Leu supplementation significantly blocked the muscle proteolysis. The mRNA expression of NF-κB, muscle atrophy F-box (MAFbx), and muscle ring finger 1 (MuRF1) was upregulated by the LPS challenge in gastrocnemius muscles, but was downregulated by Leu supplementation. Interestingly, when muscles from the LPS-challenged rats were incubated with Leu in vitro, proteasome-, calpain-, and cathepsin-L-dependent muscle proteolysis and NF-κB activity were decreased. Collectively, the data suggest that Leu supplementation could inhibit excessive skeletal muscle degradation, as well as enhance protein synthesis and, thus, attenuate the negative effects caused by the LPS-induced immune challenge.
骨骼肌萎缩是指当蛋白质降解超过蛋白质合成时发生的肌肉质量下降。亮氨酸（Leu）是动物营养中一种必需的支链氨基酸，可调节骨骼肌蛋白质代谢。进行了两项实验，以评估亮氨酸是否可以通过调节骨骼肌蛋白质合成和降解来减轻脂多糖（LPS）诱导的骨骼肌萎缩。总共24只大鼠被随机分为三组（n = 8）：（1）未受挑战的对照组；（2）LPS挑战对照组；（3）LPS + 3.0%亮氨酸组。在整个试验过程中，给大鼠喂食对照或补充亮氨酸的（用3.0%亮氨酸替代部分酪蛋白）日粮，并在第6、11、16和21天腹腔注射无菌生理盐水或LPS。在第22天早晨，采集血清样本，然后处死大鼠进行肝脏和肌肉分析。还测量了免疫挑战大鼠肌肉的体外蛋白质降解、核因子-κB（NF-κB）活性和蛋白水解酶活性。我们的结果表明，LPS挑战不仅导致血清白细胞介素-1和肝脏C反应蛋白（CRP）浓度升高，还导致平均每日体重增加和肌纤维直径减小。然而，日粮中添加亮氨酸减轻了CRP水平的升高和肌纤维直径的减小。重要的是，LPS挑战导致肌肉蛋白水解率显著升高，但日粮中补充亮氨酸显著阻断了肌肉蛋白水解。LPS挑战使腓肠肌中NF-κB、肌肉萎缩F盒（MAFbx）和肌肉环形指蛋白1（MuRF1）的mRNA表达上调，但亮氨酸补充使其下调。有趣的是，当将LPS挑战大鼠的肌肉在体外与亮氨酸一起孵育时，蛋白酶体、钙蛋白酶和组织蛋白酶L依赖性肌肉蛋白水解以及NF-κB活性降低。总体而言，数据表明补充亮氨酸可以抑制骨骼肌过度降解，以及增强蛋白质合成，从而减轻LPS诱导的免疫挑战所造成 的负面影响。
