Dysregulated Lipid Transport Proteins Correlate With Pathogenesis and Outcome in Severe Alcoholic Hepatitis

Severe alcoholic hepatitis (SAH) has high mortality. Dysregulated lipid transport and metabolism in liver/macrophages contributes to disease pathophysiology. Paraoxonase/arylesterase 1 (PON1), a liver‐specific enzyme, inhibits oxidation of phospholipids and prevents lipid‐mediated oxidative damage....

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Published in:Hepatology communications 2019-12, Vol.3 (12), p.1598-1625
Main Authors: Maras, Jaswinder Singh, Das, Sukanta, Bhat, Adil, Kumar Vyas, Ashish, Yadav, Gaurav, Chaudhary, Sudrishti, Sukriti, Sukriti, Gupta, Abhishak C., Bihari, Chagan, Mahiwall, Rakhi, Sarin, Shiv Kumar
Format: Article
Language:English
Subjects:
Alcohol
Antigens
Apoptosis
Biosynthesis
Cholesterol
Fatty acids
Hepatitis
Homeostasis
Inflammation
Lipid peroxidation
Lipids
Liver cirrhosis
Liver diseases
Low density lipoprotein
Metabolism
Mortality
Original
Oxidation
Oxidative stress
Pathogenesis
Proteins
Studies
Tumor necrosis factor-TNF
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Summary:Severe alcoholic hepatitis (SAH) has high mortality. Dysregulated lipid transport and metabolism in liver/macrophages contributes to disease pathophysiology. Paraoxonase/arylesterase 1 (PON1), a liver‐specific enzyme, inhibits oxidation of phospholipids and prevents lipid‐mediated oxidative damage. However, its functional contribution in macrophage‐mediated hepatic injury warrants elucidation. Plasma proteome of patients with SAH (n = 20), alcoholic cirrhosis (n = 20), and healthy controls was analyzed. Dysregulated pathways were identified, validated, and correlated with severity and outcomes in 200 patients with SAH. Tohoku‐Hospital‐Pediatrics‐1 (THP1)‐derived macrophages were treated with plasma from study groups in the presence/absence of recombinant PON1 and the phenotype; intracellular lipid bodies and linked functions were evaluated. In patients with SAH, 208 proteins were >1.5 fold differentially regulated (32 up‐regulated and 176 down‐regulated; P 
ISSN:2471-254X
2471-254X
DOI:10.1002/hep4.1438