Department of Animal Science, Texas A&M University, College Station, TX 77843, USA.
J Anim Sci. 2024 Jan 3;102. doi: 10.1093/jas/skae141.
The mechanistic target of rapamycin (mTOR) cell signaling pathway serves as the central mechanism for the regulation of tissue protein synthesis and growth. We recently reported that supplementing 1% glycine to corn- and soybean meal-based diets enhanced growth performance between weaning and market weights in pigs with intrauterine growth restriction (IUGR). Results of recent studies have revealed an important role for glycine in activating mTOR and protein synthesis in C2C12 muscle cells. Therefore, the present study tested the hypothesis that dietary glycine supplementation enhanced the mTOR cell signaling pathway in skeletal muscle and other tissues of IUGR pigs. At weaning (21 d of age), IUGR pigs and litter mates with normal birth weights (NBW) were assigned randomly to one of the two groups: supplementation with either 1% glycine or 1.19% l-alanine (isonitrogenous control) to a corn- and soybean meal-based diet. Tissues were obtained from the pigs within 1 wk after the feeding trial ended at 188 d of age to determine the abundances of total and phosphorylated forms of mTOR and its two major downstream proteins: eukaryotic initiation factor 4E-binding protein-1 (4EBP1) and ribosomal protein S6 kinase-1 (p70S6K). Results showed that IUGR decreased (P < 0.05) the abundances of both total and phosphorylated mTOR, 4EBP1, and p70S6K in the gastrocnemius muscle and jejunum. In the longissimus lumborum muscle of IUGR pigs, the abundances of total mTOR did not differ (P > 0.05) but those for phosphorylated mTOR and both total and phosphorylated 4EBP1 and p70S6K were downregulated (P < 0.05), when compared to NBW pigs. These adverse effects of IUGR in the gastrocnemius muscle, longissimus lumborum muscle, and jejunum were prevented (P < 0.05) by dietary glycine supplementation. Interestingly, the abundances of total or phosphorylated mTOR, 4EBP1, and p70S6K in the liver were not affected (P > 0.05) by IUGR or glycine supplementation. Collectively, our findings indicate that IUGR impaired the mTOR cell signaling pathway in the tissues of pigs and that adequate glycine intake was crucial for maintaining active mTOR-dependent protein synthesis for the growth and development of skeletal muscle.
雷帕霉素靶蛋白（mTOR）细胞信号通路作为调节组织蛋白合成和生长的中央机制。我们最近报道，在宫内生长受限（IUGR）的猪中，用 1%甘氨酸补充玉米和豆粕基础日粮可以提高断奶至上市体重期间的生长性能。最近的研究结果表明，甘氨酸在激活 C2C12 肌肉细胞中的 mTOR 和蛋白质合成中起重要作用。因此，本研究检验了以下假设：日粮甘氨酸补充增强了 IUGR 猪骨骼肌和其他组织中的 mTOR 细胞信号通路。在断奶（21 日龄）时，将 IUGR 猪和具有正常出生体重（NBW）的同窝仔猪随机分配到两组中的一组：用 1%甘氨酸或 1.19%丙氨酸（等氮对照）补充到玉米和豆粕基础日粮中。在 188 日龄饲养试验结束后 1 周内从猪中获得组织，以确定总 mTOR 和其两种主要下游蛋白：真核起始因子 4E 结合蛋白 1（4EBP1）和核糖体蛋白 S6 激酶 1（p70S6K）的磷酸化形式的丰度。结果表明，IUGR 降低（P < 0.05）了腓肠肌和空肠中总 mTOR 和磷酸化 mTOR、4EBP1 和 p70S6K 的丰度。与 NBW 猪相比，IUGR 猪的腰最长肌中总 mTOR 的丰度没有差异（P > 0.05），但磷酸化 mTOR 以及总 4EBP1 和 p70S6K 的丰度均下调（P < 0.05）。日粮甘氨酸补充可预防 IUGR 对腓肠肌、腰最长肌和空肠的这些不利影响（P < 0.05）。有趣的是，IUGR 或甘氨酸补充对肝脏中总 mTOR 或磷酸化 mTOR、4EBP1 和 p70S6K 的丰度没有影响（P > 0.05）。总之，我们的研究结果表明，IUGR 损害了猪组织中的 mTOR 细胞信号通路，而摄入足够的甘氨酸对于维持骨骼肌生长和发育所需的活跃的 mTOR 依赖性蛋白质合成至关重要。
