{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T19:41:11Z","timestamp":1781725271677,"version":"3.54.5"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>G protein\u2010coupled receptors (GPCRs) are important potential drug targets for the treatment of metabolic disorders. The D2 dopamine receptor (DRD2), a GPCR receptor, is a member of the dopamine receptor family. However, the role of DRD2 in regulating lipid metabolism, especially in hepatic steatosis, is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eight\u2010week male mice were fed HFHC\/MCD to induce the MASH model. AAV2\/8 containing the TBG promoter was used to knock down and overexpress DRD2 in mouse liver. Co\u2010immunoprecipitation, Western lotting, immunofluorescence, and immunohistochemistry were used to investigate the mechanisms and screen DRD2 antagonists.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The study found that activation of PKC leads to the elevation and internalisation of DRD2 in a high\u2010fat environment. Knockdown of DRD2 in mouse liver can effectively interfere with the progression of MASH, while overexpression of DRD2 significantly aggravates the process of MASH. The study on the mechanism of DRD2 regulating lipid metabolism found that the internalisation of DRD2 could lead to dephosphorylation of pAKT (T308) by binding to \u03b2\u2010arrestin2 and pAKT, thereby inducing ubiquitin\u2010dependent degradation of AMPK and exacerbating steatosis. L\u2010741626, a DRD2 antagonist, was found to interfere with the internalisation of DRD2 in a high\u2010fat environment. It has been shown that L\u2010741626 can treat MASH by regulating the AKT\u2010AMPK signalling axis in\u00a0vitro and in\u00a0vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In conclusion, this study demonstrated that internalisation of DRD2 in a high\u2010fat environment aggravated MASH progression through the AKT\u2010AMPK signalling axis. Furthermore, L\u2010741626, as a DRD2 antagonist, has the potential to treat MASH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70053","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T17:30:51Z","timestamp":1741714251000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>DRD2\u2010<\/scp>\n                    Mediated\n                    <scp>AMPK<\/scp>\n                    Ubiquitination Regulates the Occurrence of Hepatic Steatosis"],"prefix":"10.1111","volume":"45","author":[{"given":"Peng","family":"Ma","sequence":"first","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Ou","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junze","family":"Cai","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanli","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1794-7861","authenticated-orcid":false,"given":"Yu","family":"Ou","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.012"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1087260"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32511-3"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.06.003"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2021.01.003"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2011.00038"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.05.012"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119364"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.13437"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.09.032"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.58322"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408319200"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2019.02.005"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.168575"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22815"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.03.005"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.95"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3739"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05721-4"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2379-5"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.663102"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-023-08610-2"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M023382"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-020-0404-9"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.07.023"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-021-04219-w"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.10.009"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.03.009"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2022.110250"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2016.16"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b17-00724"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm9600712"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2006.10.076"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70053","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.70053","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:34:58Z","timestamp":1772973298000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,7]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/liv.70053"],"URL":"https:\/\/doi.org\/10.1111\/liv.70053","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,7]]},"assertion":[{"value":"2024-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70053"}}