title: Global Liver Proteome Analysis Using iTRAQ Reveals AMPK-mTOR-Autophagy Signaling Is Altered by Intrauterine Growth Restriction in Newborn Piglets.
abstract: Intrauterine growth restriction (IUGR) impairs fetal growth and development, perturbs nutrient metabolism, and increases the risk of developing diseases in postnatal life. However, the underlying mechanisms by which IUGR affects fetal liver development and metabolism remain incompletely understood. Here, we applied a high-throughput proteomics approach and biochemical analysis to investigate the impact of IUGR on the liver of newborn piglets. As a result, we identified 78 differentially expressed proteins in the three biological replicates, including 31 significantly up-regulated proteins and 47 significantly down-regulated proteins. Among them, a majority of differentially expressed proteins were related to nutrient metabolism and mitochondrial function. Additionally, many significantly down-regulated proteins participated in the mTOR signaling pathway and the phagosome maturation signaling pathway. Further analysis suggested that glucose concentration and hepatic glycogen storage were both reduced in IUGR newborn piglets, which may contribute to AMPK activation and mTORC1 inhibition. However, AMPK activation and mTORC1 inhibition failed to induce autophagy in the liver of IUGR neonatal pigs. A possible reason is that PP2Ac, a potential candidate in autophagy regulation, is significantly down-regulated in the liver of IUGR newborn piglets. These findings may provide implications for preventing and treating IUGR in human beings and domestic animals.
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Baisheng
authors.initials: B
authors.lastname: Long
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Yin
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Fan
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Guokai
authors.initials: G
authors.lastname: Yan
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Zhichang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Xiuzhi
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Chen
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Xingya
authors.initials: X
authors.lastname: Yang
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.affiliation: College of Animal Sciences and Technology, Huazhong Agricultural University , Wuhan, 430070 Hubei, China.|The Cooperative Innovation Center for Sustainable Pig Production , Wuhan 430070, Hubei, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Yan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001343:Autophagy; D002853:Chromatography, Liquid; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D058977:Molecular Sequence Annotation; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D020543:Proteome; D006003:Glycogen; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D054648:Protein Phosphatase 2; D005947:Glucose
keywords: AMPK; IUGR; PP2Ac; autophagy; mTOR; piglets; proteomics