Liu Yulan, Wang Xiuying, Leng Weibo, Pi Dingan, Tu Zhixiao, Zhu Huiling, Shi Haifeng, Li Shuang, Hou Yongqing, Hu Chien-An Andy
1 Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan, People's Republic of China.
2 Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Innate Immun. 2017 Jan;23(1):34-43. doi: 10.1177/1753425916673443. Epub 2016 Oct 22.
Infection and inflammation can result in the rapid loss of muscle mass and myofibrillar proteins (muscle atrophy). In addition, aspartate (Asp) is necessary for protein synthesis in mammalian cells. We hypothesized that Asp could attenuate LPS-induced muscle atrophy in a piglet model. Twenty-four weaning piglets were allotted to four treatments, including non-challenged control, LPS challenged control, LPS+0.5% Asp and LPS+1.0% Asp. On d 21, the piglets were injected with i.p. injection of LPS (100 ug/kg BM) or saline. At 4 h post-injection, blood, gastrocnemius and longissimus dorsi muscles samples were collected for biochemical and molecular analyses. Asp decreased the concentrations of cortisol and glucagon in plasma. In addition, Asp increased protein and RNA contents in muscles, and decreased mRNA expression of muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1). Moreover, Asp decreased phosphorylation of AMPKα but increased phosphorylation of Akt and Forkhead Box O (FOXO) 1 in the muscles. Our results indicate that Asp suppresses LPS-induced MAFbx and MuRF1 expression via activation of Akt signaling, and inhibition of AMPKα and FOXO1 signaling.
感染和炎症可导致肌肉质量和肌原纤维蛋白迅速流失(肌肉萎缩)。此外,天冬氨酸(Asp)是哺乳动物细胞蛋白质合成所必需的。我们假设Asp可以减轻仔猪模型中脂多糖(LPS)诱导的肌肉萎缩。将24头断奶仔猪分配到四种处理组,包括未受挑战的对照组、LPS挑战对照组、LPS + 0.5% Asp组和LPS + 1.0% Asp组。在第21天,给仔猪腹腔注射LPS(100 μg/kg体重)或生理盐水。注射后4小时,采集血液、腓肠肌和背最长肌样本进行生化和分子分析。Asp降低了血浆中皮质醇和胰高血糖素的浓度。此外,Asp增加了肌肉中的蛋白质和RNA含量,并降低了肌肉萎缩F盒(MAFbx)和肌肉环指蛋白1(MuRF1)的mRNA表达。此外,Asp降低了肌肉中AMPKα的磷酸化水平,但增加了Akt和叉头盒O(FOXO)1的磷酸化水平。我们的结果表明,Asp通过激活Akt信号通路以及抑制AMPKα和FOXO1信号通路来抑制LPS诱导的MAFbx和MuRF1表达。