{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:57:08Z","timestamp":1784296628855,"version":"3.55.0"},"reference-count":50,"publisher":"The Korean Association for the Study of the Liver","issue":"2","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070655"],"award-info":[{"award-number":["82070655"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020771","name":"Young Scientists Fund of the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82000605"],"award-info":[{"award-number":["82000605"]}],"id":[{"id":"10.13039\/501100020771","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["e-cmh.org"],"crossmark-restriction":true},"short-container-title":["Clin Mol Hepatol"],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"<jats:p>Background\/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation.Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-\/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation.Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-\/- and WT mice, respectively. GOLM1-\/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1\u03b2 (IL-1\u03b2) in a dose-dependent manner. Finally, we confirmed that IL-1\u03b2, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs.Conclusions: In MASH livers, upregulation of GOLM1 by IL-1\u03b2 increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.<\/jats:p>","DOI":"10.3350\/cmh.2024.0657","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T23:55:28Z","timestamp":1733874928000},"page":"409-425","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in metabolic dysfunction-associated steatohepatitis livers"],"prefix":"10.3350","volume":"31","author":[{"given":"Yi-Tong","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Qing","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Chen","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-He","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-Rui","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-2802","authenticated-orcid":true,"given":"Jing","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0952-9990","authenticated-orcid":true,"given":"Jin-Hong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1902","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.24"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2014.140"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2023.155774"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1598751"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01198-0"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2015.11.008"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.06.021"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041183"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.3390\/jcm7110458"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-023-09458-3"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-017-8655-y"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0009-6"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1186\/2045-3701-4-76"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.11.013"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110712"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2022.100259"},{"key":"ref17","first-page":"10567","volume-title":"CHIP ameliorates nonalcoholic fatty liver disease via promoting K63- and K27-linked STX17 ubiquitination to facilitate autophagosome-lysosome fusion. 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