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Dietary protein-induced hepatic IGF-1 secretion mediated by PPAR? activation.

ABSTRACT: 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 PPAR? increased with the increasing AA concentration in the culture. The PPAR? activator troglitazone increased IGF-1 gene expression and secretion in a dose dependent manner. Furthermore, inhibition of PPAR? 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 PPAR?, 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 PPAR?. In summary, PPAR? plays an important role in the regulation of IGF-1 secretion and gene expression in response to dietary protein.

SUBMITTER: Wan X

PROVIDER: S-EPMC5336265 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ activation.

Wan Xiaojuan X Wang Songbo S Xu Jingren J Zhuang Lu L Xing Kongping K Zhang Mengyuan M Zhu Xiaotong X Wang Lina L Gao Ping P Xi Qianyun Q Sun Jiajie J Zhang Yongliang Y Li Tiejun T Shu Gang G Jiang Qingyan Q

PloS one 20170303 3

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 ...[more]

PMID: 28257428

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Dataset Information

Dietary protein-induced hepatic IGF-1 secretion mediated by PPAR? activation.

Publications

Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ activation.

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