雷帕霉素(mTOR)细胞信号通路的机制靶标是调节组织蛋白合成和生长的核心机制。我们最近报道,在基于玉米和豆粕的日粮中补充1%甘氨酸可提高宫内生长受限(IUGR)猪断奶和市场体重之间的生长性能。最近的研究结果揭示了甘氨酸在C2C12肌细胞中激活mTOR和蛋白质合成中的重要作用。因此,本研究检验了以下假设:饮食中补充甘氨酸可增强IUGR猪骨骼肌和其他组织中的mTOR细胞信号通路.断奶时(21日龄),将具有正常出生体重(NBW)的IUGR猪和产仔配偶随机分为两组之一:在玉米和豆粕饮食中补充1%甘氨酸或1.19%L-丙氨酸(等氮对照)。饲喂试验在188日龄结束后1周内从猪中获得组织,以确定mTOR及其两种主要下游蛋白的总和磷酸化形式的丰度:真核起始因子4E结合蛋白1(4EBP1)和核糖体蛋白S6激酶-1(p70S6K)。结果表明,IUGR降低(P<0.05)总和磷酸化mTOR的丰度,4EBP1,而p70S6K在腓肠肌和空肠。在IUGR猪的腰肌中,总mTOR的丰度没有差异(P>0.05),但磷酸化mTOR以及总和磷酸化4EBP1和p70S6K的丰度均下调(P<0.05),与NBW猪相比。这些不利影响的IUGR在腓肠肌,腰最长肌,饮食中补充甘氨酸可预防空肠和空肠(P<0.05)。有趣的是,总或磷酸化mTOR的丰度,肝脏中的4EBP1和p70S6K不受IUGR或甘氨酸补充的影响(P>0.05)。总的来说,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,充足的甘氨酸摄入对于维持骨骼肌生长和发育中mTOR依赖性蛋白合成的活性至关重要.
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.
Soybean meal is the major source of dietary protein for growing pigs in many regions of the world, including North America, South America, and Asia. However, this conventional feedstuff is recognized to be severely deficient in glycine (the most abundant amino acid in the bodies of animals, including pigs). Compared to pigs with normal birth weights (NBW), pigs with intrauterine growth restriction (IUGR) have a lower ability to synthesize glycine and reduced growth performance between weaning and market weights. Results of recent studies with cultured muscle cells have revealed that glycine stimulates the mechanistic target of rapamycin (mTOR) cell signaling pathway (the master activator of initiation of protein synthesis in tissues) to promote protein synthesis and cell growth. There is also evidence that the mTOR pathway is impaired in the skeletal muscle of young IUGR pigs. Thus, dietary glycine supplementation may play an important role in maintaining an active mTOR cell signaling pathway for the growth of tissues, particularly skeletal muscle. Results of this study indicated that market-weight IUGR pigs had lower abundances of both total and phosphorylated mTOR, as well as its downstream target proteins in the gastrocnemius muscle, longissimus lumborum muscle, and jejunum, when compared with NBW pigs. In contrast, neither IUGR nor glycine supplementation affected the mTOR cell signaling pathway in the liver of pigs. Taken together, these novel findings indicate that IUGR pigs have insufficient cell signaling via the mTOR cell pathway in a tissue-specific manner during their growing-finishing phases of development and that this negative impact of IUGR can be mitigated by supplementing corn- and soybean meal-based diets with 1% glycine.