Global Liver Proteome Analysis Using iTRAQ Reveals AMPK–mTOR–Autophagy Signaling Is Altered by Intrauterine Growth Restriction in Newborn Piglets

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.