title: Dietary protein-induced hepatic IGF-1 secretion mediated by PPARγ 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 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.
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wan
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Songbo
authors.initials: S
authors.lastname: Wang
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Jingren
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhuang
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Kongping
authors.initials: K
authors.lastname: Xing
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Zhang
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Qianyun
authors.initials: Q
authors.lastname: Xi
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Jiajie
authors.initials: J
authors.lastname: Sun
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Subtropical Agro-ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, Hunan, PR China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Li
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Shu
authors.affiliation: College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou, China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002839:Chromans / Q000008:administration & dosage; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage*; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D047495:PPAR gamma / Q000097:blood; D015398:Signal Transduction; D013552:Swine; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D045162:Thiazolidinediones / Q000008:administration & dosage; D000077288:Troglitazone
chemical_list: D002839:Chromans; D004044:Dietary Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D047495:PPAR gamma; D045162:Thiazolidinediones; D007334:Insulin-Like Growth Factor I; D058570:TOR Serine-Threonine Kinases; D000077288:Troglitazone