{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:34:19Z","timestamp":1747182859387,"version":"3.40.5"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01BX005093"],"award-info":[{"award-number":["I01BX005093"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01AA025907"],"award-info":[{"award-number":["R01AA025907"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Previously, we demonstrated that <jats:italic>Spp1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibit a greater susceptibility to alcohol\u2010induced liver injury than wild\u2010type (WT) mice. Notably, alcohol triggers the expression of osteopontin (encoded by <jats:italic>SPP1<\/jats:italic>) in hepatocytes. However, the specific role of hepatocyte\u2010derived SPP1 in either mitigating or exacerbating alcohol\u2010associated liver disease (AALD) has yet to be elucidated. We hypothesized that hepatocyte\u2010derived SPP1 plays a role in AALD by modulating the regulation of steatosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed hepatic SPP1 expression using four publicly available datasets from patients with alcoholic hepatitis (AH). Additionally, we examined SPP1 expression in the livers of WT mice subjected to either a control or ethanol Lieber\u2010DeCarli (LDC) diet for 6\u2009weeks. We compared the relationship between SPP1 expression and significantly dysregulated genes in AH with controls using correlation and enrichment analyses. To investigate the specific impact of hepatocyte\u2010derived SPP1, we generated hepatocyte\u2010specific <jats:italic>Spp1<\/jats:italic> knock\u2010out (<jats:italic>Spp1<\/jats:italic><jats:sup>\u0394Hep<\/jats:sup>) mice and subjected them to either a control or ethanol Lieber\u2010DeCarli diet for 6\u2009weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alcohol induced hepatic SPP1 expression in both humans and mice. Our analysis, focusing on genes correlated with <jats:italic>SPP1<\/jats:italic>, revealed an enrichment of fatty acid oxidation (FAO) in three datasets, and peroxisome proliferator\u2010activated receptor signaling in one dataset. Notably, FAO genes correlating with <jats:italic>SPP1<\/jats:italic> were downregulated in patients with AH. Ethanol\u2010fed WT mice exhibited higher serum\u2010free fatty acids (FFAs), adipose tissue lipolysis, and hepatic fatty acid (FA) transporters. In contrast, ethanol\u2010fed <jats:italic>Spp1<\/jats:italic><jats:sup>\u0394Hep<\/jats:sup> mice displayed lower liver triglycerides, FFAs, and serum alanine transaminase and greater FAO gene expression than WT mice, indicating a protective effect against AALD. Primary hepatocytes from <jats:italic>Spp1<\/jats:italic><jats:sup>\u2206Hep<\/jats:sup> mice exhibited heightened expression of genes encoding proteins involved in FAO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Alcohol induces the expression of SPP1 in hepatocytes, leading to impaired FAO and contributing to the development of AALD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.15304","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T02:40:30Z","timestamp":1710902430000},"page":"781-794","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ablation of secreted phosphoprotein\u20101 in hepatocytes increases fatty acid oxidation and ameliorates alcohol\u2010associated liver disease"],"prefix":"10.1111","volume":"48","author":[{"given":"Sukanta","family":"Das","sequence":"first","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nithyananthan","family":"Subramaniyam","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Al\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai Santosh Babu","family":"Komakula","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuolun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romain","family":"Desert","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dipti","family":"Athavale","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Magdaleno","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ines","family":"Barahona","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Lantvit","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grace","family":"Guzman","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-6804","authenticated-orcid":false,"given":"Natalia","family":"Nieto","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Illinois at Chicago  Chicago Illinois USA"},{"name":"Division of Gastroenterology and Hepatology, Department of Medicine University of Illinois at Chicago  Chicago Illinois USA"},{"name":"Research and Development Service Jesse Brown Veterans Affairs Medical Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-301146"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.04.014"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-310752"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4760"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.05.041"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103244"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00465.2011"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1793"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i37.4974"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.05.012"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01643"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504460200"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.552141"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26931"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00014.2013"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2006.02416.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i40.14855"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1982.tb05017.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1116"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.12.008"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840030215"},{"volume-title":"GeneReviews((R))","year":"1993","author":"Merritt J.L.","key":"e_1_2_9_23_1"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26521"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21427"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20150295"},{"key":"e_1_2_9_27_1","first-page":"147","article-title":"Alcoholic liver disease: pathogenesis and current management","volume":"38","author":"Osna N.A.","year":"2017","journal-title":"Alcohol Research: Current Reviews"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28044-x"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.116"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035612"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.4103\/0253-7613.96297"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0301086"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31582"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom7010016"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-206326"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2011.02.014"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.649140"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i36.12908"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.11.017"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz240"}],"container-title":["Alcohol, Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.15304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T14:56:27Z","timestamp":1715007387000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.15304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,19]]},"references-count":39,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/acer.15304"],"URL":"https:\/\/doi.org\/10.1111\/acer.15304","archive":["Portico"],"relation":{},"ISSN":["2993-7175","2993-7175"],"issn-type":[{"type":"print","value":"2993-7175"},{"type":"electronic","value":"2993-7175"}],"subject":[],"published":{"date-parts":[[2024,3,19]]},"assertion":[{"value":"2023-10-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}