Multiomics Approach Captures Hepatic Metabolic Network Altered by Chronic Ethanol Administration

Authors

Isin Tuna Sakallioglu, University of Nebraska-Lincoln
Bridget Tripp, University of Nebraska-Lincoln
Jacy Kubik, University of Nebraska Medical Center
Carol A. Casey, University of Nebraska Medical CenterFollow
Paul G. Thomes, University of Nebraska Medical CenterFollow
Robert Powers, University of Nebraska - LincolnFollow

Date of this Version

12-23-2022

Citation

Sakallioglu, I.T.; Tripp, B.; Kubik, J.; Casey, C.A.; Thomes, P.; Powers, R. Multiomics Approach Captures Hepatic Metabolic Network Altered by Chronic Ethanol Administration. Biology 2023, 12, 28. https://doi.org/10.3390/ biology12010028

Comments

Open access.

Abstract

Using a multiplatform and multiomics approach, we identified metabolites, lipids, proteins, and metabolic pathways that were altered in the liver after chronic ethanol administration. A functional enrichment analysis of the multiomics dataset revealed that rats treated with ethanol experienced an increase in hepatic fatty acyl content, which is consistent with an initial development of steatosis. The nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography–mass spectrometry (LC-MS) metabolomics data revealed that the chronic ethanol exposure selectively modified toxic substances such as an increase in glucuronidation tyramine and benzoyl; and a depletion in cholesterol-conjugated glucuronides. Similarly, the lipidomics results revealed that ethanol decreased diacylglycerol, and increased triacylglycerol, sterol, and cholesterol biosynthesis. An integrated metabolomics and lipidomics pathway analysis showed that the accumulation of hepatic lipids occurred by ethanol modulation of the upstream lipid regulatory pathways, specifically glycolysis and glucuronides pathways. A proteomics analysis of lipid droplets isolated from control EtOH-fed rats and a subsequent functional enrichment analysis revealed that the proteomics data corroborated the metabolomic and lipidomic findings that chronic ethanol administration altered the glucuronidation pathway.