AMPK-mTOR pathway is involved in glucose-modulated amino acid sensing and utilization in the mammary glands of lactating goats
AMPK-mTOR pathway is involved in glucose-modulated amino acid sensing and utilization in the mammary glands of lactating goats
复制标题
AMPK-mTOR 通路参与泌乳山羊乳腺中葡萄糖调节的氨基酸传感和利用
DOI：
10.1186/s40104-020-0434-6
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发表时间：
2020-02-14
影响因子：
7
通讯作者：
Liu, Jianxin
中科院分区：
文献类型：
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作者：
Cai, Jie;Wang, Diming;Liu, Jianxin
背景局部供应的能量产生的营养物质，如葡萄糖，似乎会影响乳腺（MG）的牛奶成分的合成。因此，本研究旨在探讨局部可利用MG葡萄糖供应（LMGS）对泌乳奶山羊MG氨基酸（AA）感受和利用的影响。通过阴部外动脉向MG中注入6种剂量的葡萄糖（0、20、40、60、80和100 g/d），以研究乳腺AA摄取和利用的剂量依赖性变化（实验1）以及AMPK-mTOR通路的mRNA和蛋白表达的变化（实验2）。结果实验1中，山羊输注60 g/d葡萄糖时，总乳AA含量最高，输注0和100 g/d葡萄糖时，总乳AA含量较低。增加LMGS二次改变牛奶蛋白中α（S2）-酪蛋白和α-乳白蛋白的百分比，其随着输注从0到60 g/d葡萄糖而增加，然后随着输注60和100 g/d葡萄糖而减少。LMGS改变了AA的可用性和乳腺内AA的利用率，反映了乳腺AA流量指数。在实验2中，LALBA在MG中的mRNA表达随着LMGS的增加而二次增加，在60 g/d葡萄糖剂量下表达最高。高葡萄糖剂量（100 g/d）激活一般控制非去阻遏2激酶，AA状态的细胞内传感器，导致总牛奶AA浓度降低。结论LMGS可能通过调节AA感觉通路、AA利用和蛋白质合成等途径影响泌乳期奶山羊MG，这些作用均由AMPK-mTOR通路驱动。
Background The local supply of energy-yielding nutrients such as glucose seems to affect the synthesis of milk components in the mammary gland (MG). Thus, our study was conducted to investigate the effects of locally available MG glucose supply (LMGS) on amino acid (AA) sensing and utilization in the MG of lactating dairy goats. Six dosages of glucose (0, 20, 40, 60, 80, and 100 g/d) were infused into the MG through the external pudendal artery to investigate the dose-dependent changes in mammary AA uptake and utilization (Exp.1) and the changes in mRNA and protein expression of the AMPK-mTOR pathway (Expt.2). Results In Exp.1, total milk AA concentration was highest when goats were infused with 60 g/d glucose, but lower when goats were infused with 0 and 100 g/d glucose. Increasing LMGS quadratically changed the percentages of alpha(S2)-casein and alpha-lactalbumin in milk protein, which increased with infusions from 0 to 60 g/d glucose and then decreased with infusions between 60 and 100 g/d glucose. The LMGS changed the AA availability and intramammary gland AA utilization, as reflected by the mammary AA flux indexes. In Exp.2, the mRNA expression of LALBA in the MG increased quadratically with increasing LMGS, with the highest expression at dose of 60 g/d glucose. A high glucose dosage (100 g/d) activated the general control nonderepressible 2 kinase, an intracellular sensor of AA status, resulting in a reduced total milk AA concentration. Conclusions Our new findings suggest that the lactating MG in dairy goats may be affected by LMGS through regulation of the AA sensory pathway, AA utilization and protein synthesis, all being driven by the AMPK-mTOR pathway.