Abstract
BackgroundParenteral nutrition (PN)-associated liver disease (PNALD) is a common and life-threatening complication in patients receiving PN. However, its definitive etiology is not yet clear. Therefore, performed proteomic analyses of human liver tissue to explore the same.MethodsLiver tissue was derived and compared across selected patients with (n = 3) /without (n = 4) PNALD via isobaric Tag for Relative and Absolute Quantitation (iTRAQ)-based quantitative proteomics. Bioinformatics analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases to explore the mechanisms of PNALD based on differentially expressed proteins (DEPs). The essential proteins that were differentially expressed between the two groups were explored and verified by western blotting.ResultsA total of 112 proteins were found to be differentially expressed, of which 73 were downregulated, and 39 were upregulated in the PNALD group. Bioinformatics analysis showed DEPs to be associated with mitochondrial oxidative phosphorylation (mainly involved in mitochondrial respiratory chain complex I assembly), hepatic glycolipid metabolism (involved primarily in glycogen formation and gluconeogenesis), and oxidative stress (mainly involved in antioxidant change).ConclusionOverall, our results indicated that mitochondrial energy metabolism impairment, hepatic glycolipid metabolism disorder, and excessive oxidative stress injury might explain the comprehensive mechanism underlying PNALD. Moreover, we have provided multiple potential targets for further exploring the PNALD mechanism.
Highlights
Parenteral nutrition (PN)-associated liver disease (PNALD) is a common and life-threatening complication in patients receiving PN
This study aimed to explore the possible mechanisms underlying the pathogenesis of Parenteral nutrition-associated liver disease (PNALD), as well as identify potential therapeutic targets by performing hepatic proteomics in patients with or without PNALD in the present study
To identify the functional classification of differentially expressed proteins (DEPs), this study performed gene ontology analysis according to their molecular functions (MF), biological processes (BP), and cellular components (CC) with the assistance of DAVID Bioinformatics Resources
Summary
Parenteral nutrition (PN)-associated liver disease (PNALD) is a common and life-threatening complication in patients receiving PN. Most biochemical abnormalities of the liver can be reversed by weaning at an early stage of PNALD, whereas most of the advanced pathophysiological changes are irreversible, resulting in cirrhosis, decompensated liver disease, liver failure, and liver carcinoma. In these patients, PNALD progresses to end-stage liver disease, requiring combined intestinal and liver transplant [6,7,8]. The pathophysiology and etiology of PNALD remain unclear, and there have been very few studies exploring the overall protein expression in liver tissue of patients with PNALD
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