Metabolic and Proteomic Responses to Long-Term Protein Restriction in a Pig Model

Protein
restriction is associated with extended lifespan and reduced
incidence and progression of multiple age-related diseases. The underlying
mechanism of metabolic and proteomic responses to the long-term dietary
protein restriction, however, has not been fully uncovered. The present
study aimed to identify the metabolic and proteomic profiles in a
low-protein diet-fed pig model. Intestinal and liver metabolomics
showed that amino acid metabolism was highly associated with dietary
protein restriction. Interestingly, blood was characterized by markedly
higher abundances of Ser, Gly, Glu, Thr, Ala, Lys, and Met levels,
and lower abundances of His, Val, and Ile levels regardless of the
age of pigs from piglets to adult pigs. Amino acid transporters might
contribute to the changed amino acid pools and serve as a feedback
regulatory mechanism in response to protein restriction. iTRAQ-based
quantitative proteomics approach identified more than 10 differently
expressed proteins in protein restricted pigs and KEGG pathway analysis
showed that significant enrichment of proteins involved in metabolic
pathways, PI3K-Akt signaling pathway, lysosome, spliceosome, oxidative
phosphorylation, phagosome, and DNA replication. Western blot analysis
further confirmed that protein restriction markedly inactivated Akt
and mTOR signals in pigs. This study indicates that dietary protein
restriction leads to a shift in the host metabolism in a pig model,
especially for amino acid metabolism. Along with proteomics, our findings
unveil potential mechanisms for integrating how protein restriction
modulates host metabolism.