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Although studies have analyzed the global protein expression in the context of alcoholic liver disease (ALD) and metabolic dysfunction\u2010associated steatotic liver disease (MASLD), none has offered specific insights on liver dysregulation at the membrane proteome level. Membrane\u2010specific profiling of metabolic and compensatory phenomena is usually overshadowed in conventional proteomic workflows. In this study, we use the Peptidisc method to isolate and compare the membrane protein (MP) content of the liver with its unique biological functions. From mice fed with an HF diet and ethanol in drinking water, we annotate over 1500 liver proteins with half predicted to have at least one transmembrane segment. Among them, we identify 106 integral MPs that are dysregulated compared to the untreated sample. Gene Ontology analysis reveals several dysregulated membrane\u2010associated processes like lipid metabolism, cell adhesion, xenobiotic processing, and mitochondrial membrane formation. Pathways related to cholesterol and bile acid transport are also mutually affected, suggesting an adaptive mechanism to counter the upcoming steatosis of the liver model. Taken together, our Peptidisc\u2010based profiling of the diet\u2010dysregulated liver provides specific insights and hypotheses into the role of the transmembrane proteome in disease development, and flags desirable MPs for therapeutic and diagnostic targeting.<\/jats:p>","DOI":"10.1002\/pmic.202300599","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T02:15:41Z","timestamp":1727144141000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sensitive Profiling of Mouse Liver Membrane Proteome Dysregulation Following a High\u2010Fat and Alcohol Diet Treatment"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7328-6124","authenticated-orcid":false,"given":"Frank","family":"Antony","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Life Sciences Institute University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zora","family":"Brough","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Life Sciences Institute University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Orangi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Al\u2010Seragi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Life Sciences Institute University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Regina  Regina Saskatchewan Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan","family":"Babu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Regina  Regina Saskatchewan Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Duong van Hoa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Life Sciences Institute University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32163"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232416226"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24097791"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2020.0100"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2009.01122.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.10.005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v5.i10.550"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2011.01472.x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105279"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000447279"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.10.037"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23280"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2015-1866"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0907"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222312808"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.4.11.1403"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200043335531"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2016.05.014"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-021-00869-6"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2021.08.017"},{"issue":"3","key":"e_1_2_9_22_1","first-page":"352","article-title":"Measurement and Clinical Usefulness of Bilirubin in Liver Disease","volume":"2","author":"Guerra Ruiz A. 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