Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ activation.
Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ activation.
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PPARγ 激活介导的膳食蛋白诱导的肝脏 IGF-1 分泌
DOI：
10.1371/journal.pone.0173174
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Jiang Q
中科院分区：
文献类型：
--
作者：
Wan X;Wang S;Xu J;Zhuang L;Xing K;Zhang M;Zhu X;Wang L;Gao P;Xi Q;Sun J;Zhang Y;Li T;Shu G;Jiang Q
膳食蛋白质或氨基酸（AA）是调节肝脏胰岛素样生长因子-1（IGF-1）表达和分泌的关键营养因子。然而，膳食蛋白质或 AA 诱导 IGF-1 表达的潜在细胞内机制仍不清楚。我们比较了饲喂正常粗蛋白（CP，20%）和低蛋白水平（LP，14%）的猪的 IGF-1 基因表达和血浆 IGF-1 水平。进行 RNA 测序 (RNA-seq) 来检测肝脏中对膳食蛋白质的反应的转录表达。结果显示，CP组血清IGF-1浓度和肝脏IGF-1 mRNA水平高于LP组。 RNA-seq分析共鉴定出1319个差异表达转录本（667个上调，652个下调），其中“氧化磷酸化”、“核糖体”、“间隙连接”、“PPAR信号通路”和“粘着斑”等术语得到丰富。此外，猪原代肝细胞和HepG2细胞模型也表明，IGF-1和PPARγ的mRNA和蛋白水平随着培养物中AA浓度的增加而增加。 PPARγ 激活剂曲格列酮以剂量依赖性方式增加 IGF-1 基因表达和分泌。此外，抑制PPARγ可有效逆转高AA浓度对HepG2细胞中IGF-1和IGFBP-1 mRNA表达的影响。此外，在高AA浓度下，HepG2细胞中IGF-1和PPARγ的蛋白水平以及mTOR的磷酸化显着增加。 mTOR 拮抗剂雷帕霉素可降低 mTOR 磷酸化。免疫沉淀结果还表明，高 AA 浓度显着增加 mTOR 和 PPARγ 的相互作用。总之，PPARγ 在调节 IGF-1 分泌和响应膳食蛋白质的基因表达方面发挥重要作用。
Dietary protein or amino acid (AA) is a crucial nutritional factor to regulate hepatic insulin-like growth factor-1 (IGF-1) expression and secretion. However, the underlying intracellular mechanism by which dietary protein or AA induces IGF-1 expression remains unknown. We compared the IGF-1 gene expression and plasma IGF-1 level of pigs fed with normal crude protein (CP, 20%) and low-protein levels (LP, 14%). RNA sequencing (RNA-seq) was performed to detect transcript expression in the liver in response to dietary protein. The results showed that serum concentrations and mRNA levels of IGF-1 in the liver were higher in the CP group than in the LP group. RNA-seq analysis identified a total of 1319 differentially expressed transcripts (667 upregulated and 652 downregulated), among which the terms “oxidative phosphorylation”, “ribosome”, “gap junction”, “PPAR signaling pathway”, and “focal adhesion” were enriched. In addition, the porcine primary hepatocyte and HepG2 cell models also demonstrated that the mRNA and protein levels of IGF-1 and PPARγ increased with the increasing AA concentration in the culture. The PPARγ activator troglitazone increased IGF-1 gene expression and secretion in a dose dependent manner. Furthermore, inhibition of PPARγ effectively reversed the effects of the high AA concentration on the mRNA expression of IGF-1 and IGFBP-1 in HepG2 cells. Moreover, the protein levels of IGF-1 and PPARγ, as well as the phosphorylation of mTOR, significantly increased in HepG2 cells under high AA concentrations. mTOR phosphorylation can be decreased by the mTOR antagonist, rapamycin. The immunoprecipitation results also showed that high AA concentrations significantly increased the interaction of mTOR and PPARγ. In summary, PPARγ plays an important role in the regulation of IGF-1 secretion and gene expression in response to dietary protein.