Profiling the Liver Membrane Proteome in the Context of Liver Disease

Alcohol consumption and high-fat diets often coincide in Western society, exerting negative synergistic effects on the liver. While many studies have demonstrated the impact of ALD and NAFLD on protein expression, none have offered a comprehensive view of the dysregulation at the level of the membrane proteome. In this study, we utilize the peptidisc and SP4 methods to isolate and compare the membrane protein content of the mouse liver with its unique biological functions. Applying the peptidisc method to mice treated with a high-fat diet and ethanol in drinking water, we identified 1,563 liver proteins, with 46% predicted to have a transmembrane segment. Among these, 106 integral membrane proteins are dysregulated compared to the untreated sample. Gene ontology analysis revealed membrane proteins associated with lipid metabolism, cell adhesion, xenobiotic processing, and mitochondrial structural formation among others. Pathways related to cholesterol and bile acid metabolism were mutually affected, suggesting a potential adaptive mechanism to counter the expected steatosis in our liver model. This peptidisc-based profiling generates global insights into the role of the transmembrane proteome in disease development, warranting further in-depth analysis on the individual contribution of the suspect dysregulated proteins.