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High-level L-Gln compromises intestinal amino acid utilization efficiency and inhibits protein synthesis by GCN2/eIF2α/ATF4 signaling pathway in piglets fed low-crude protein diets
Animal Nutrition ( IF 6.1 ) Pub Date : 2024-09-21 , DOI: 10.1016/j.aninu.2024.06.008
Jun Li, Yinfeng Chen, Yang Yang, Ying Yang, Zhenlong Wu

Gln, one of the most abundant amino acids (AA) in the body, performs a diverse range of fundamental physiological functions. However, information about the role of dietary Gln on AA levels, transporters, protein synthesis, and underlying mechanisms in vivo is scarce. The present study aimed to explore the effects of low-crude protein diet inclusion with differential doses of L-Gln on intestinal AA levels, transporters, protein synthesis, and potential mechanisms in weaned piglets. A total of 128 healthy weaned piglets (Landrace × Yorkshire) were randomly allocated into four treatments with four replicates. Pigs in the four groups were fed a low-crude protein diet containing 0%, 1%, 2%, or 3% L-Gln for 28 d. L-Gln administration markedly (linear, P < 0.05) increased Ala, Arg, Asn, Asp, Glu, Gln, His, Ile, Lys, Met, Orn, Phe, Ser, Thr, Tyr, and Val levels and promoted trypsin activity in the jejunal content of piglets. Moreover, L-Gln treatment significantly enhanced concentrations of colonic Gln and Trp, and serum Thr (linear, P < 0.01), and quadratically increased serum Lys and Phe levels (P < 0.05), and decreased plasma Glu, Ile, and Leu levels (linear, P < 0.05). Further investigation revealed that L-Gln administration significantly upregulated Atp1a1, Slc1a5, Slc3a2, Slc6a14, Slc7a5, Slc7a7, and Slc38a1 relative expressions in the jejunum (linear, P < 0.05). Additionally, dietary supplementation with L-Gln enhanced protein abundance of general control nonderepressible 2 (GCN2, P = 0.010), phosphorylated eukaryotic initiation factor 2 subunit alpha (eIF2α, P < 0.001), and activating transcription factor 4 (ATF4) in the jejunum of piglets (P = 0.008). These results demonstrated for the first time that a low crude protein diet with high-level L-Gln inclusion exhibited side effects on piglets. Specifically, 2% and 3% L-Gln administration exceeded the intestinal utilization capacity and compromised the jejunal AA utilization efficiency, which is independent of digestive enzyme activities. A high level of L-Gln supplementation would inhibit protein synthesis by GCN2/eIF2α/ATF4 signaling in piglets fed low-protein diets, which, in turn, upregulates certain AA transporters to maintain AA homeostasis.

中文翻译:


高水平 L-Gln 影响低粗蛋白日粮仔猪肠道氨基酸利用效率并抑制 GCN2/eIF2α/ATF4 信号通路的蛋白质合成



Gln 是体内最丰富的氨基酸 (AA) 之一,执行多种基本生理功能。然而,关于膳食 Gln 对 AA 水平、转运蛋白、蛋白质合成和体内潜在机制的作用的信息很少。本研究旨在探讨低粗蛋白日粮中添加不同剂量 L-Gln 对断奶仔猪肠道 AA 水平、转运蛋白、蛋白质合成和潜在机制的影响。共有 128 头健康断奶仔猪(长白×约克郡)被随机分配到 4 个处理中,每个处理 4 个重复。4 组猪饲喂 0% 、 1% 、 2% 或 3% L-Gln 的低粗蛋白日粮 28 d。L-Gln 给药显著提高仔猪空肠内容物中 Ala、Arg、Asn、Asp、Glu、Gln、His、Ile、Lys、Met、Orn、Phe、Ser、Thr、Tyr 和 Val 水平,并促进胰蛋白酶活性。此外,L-Gln 处理显著提高结肠 Gln 和 Trp 浓度,以及血清 Thr 浓度 (线性,P < 0.01),血清 Lys 和 Phe 水平二次升高 (P < 0.05),降低血浆 Glu 、 Ile 和 Leu 水平 (线性,P < 0.05)。进一步研究显示,L-Gln 给药显著上调空肠中 Atp1a1 、 Slc1a5 、 Slc3a2 、 Slc6a14 、 Slc7a5 、 Slc7a7 和 Slc38a1 的相对表达 (线性,P < 0.05)。此外,日粮中添加 L-Gln 增强了仔猪空肠中一般对照不可抑制因子 2 (GCN2,P = 0.010)、磷酸化真核起始因子 2 亚基 α (eIF2α,P < 0.001) 和激活转录因子 4 (ATF4) 的蛋白质丰度 (P = 0.008)。 这些结果首次表明,含有高水平 L-Gln 的低粗蛋白日粮对仔猪表现出副作用。具体来说,2% 和 3% L-Gln 给药超过了肠道利用能力,并损害了空肠 AA 利用效率,这与消化酶活性无关。在饲喂低蛋白日粮的仔猪中,高水平的 L-Gln 补充剂会抑制 GCN2/eIF2α/ATF4 信号传导的蛋白质合成,这反过来又会上调某些 AA 转运蛋白以维持 AA 稳态。
更新日期:2024-09-21
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