{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T05:06:36Z","timestamp":1793336796257,"version":"4.5.0"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2022R1A2C1011069"],"award-info":[{"award-number":["NRF-2022R1A2C1011069"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["NRF-2022R1A2C1011069"],"award-info":[{"award-number":["NRF-2022R1A2C1011069"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HR18C001204"],"award-info":[{"award-number":["HR18C001204"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"award":["HR18C001204"],"award-info":[{"award-number":["HR18C001204"]}],"id":[{"id":"https:\/\/ror.org\/00fdzyk40","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic triglyceride accumulation in the setting of obesity and insulin resistance. Although apolipoprotein C-III (APOC3) is a well-established regulator of plasma triglyceride metabolism, its hepatocyte-intrinsic role in intracellular lipid accumulation remains unclear. In this study, we investigated whether APOC3 contributes to hepatocellular triglyceride synthesis during early metabolic dysfunction. In 6-week-old db\/db mice, early hepatic lipid accumulation was observed without detectable fibrosis. Transcriptomic profiling identified APOC3 as an upregulated gene associated with lipid metabolic pathways, and its hepatic upregulation was confirmed at both mRNA and protein levels. Gain- and loss-of-function experiments in HepG2 cells demonstrated that APOC3 overexpression significantly increased intracellular triglyceride content, whereas APOC3 knockdown reduced triglyceride accumulation. Mechanistically, APOC3 selectively regulated diacylglycerol acyltransferase 2 (DGAT2), which catalyzes the final step of triglyceride synthesis, without significantly affecting major lipogenic transcription factors. Furthermore, under de novo lipogenesis-inducing conditions triggered by the liver X receptor agonist T0901317 and insulin, APOC3 markedly amplified DGAT2 expression and triglyceride accumulation. Collectively, these findings suggest a hepatocyte-intrinsic role for APOC3 in promoting triglyceride accumulation through DGAT2-dependent mechanisms. The APOC3\u2013DGAT2 axis may represent a relevant pathway contributing to hepatic lipid accumulation in metabolic liver disease.<\/jats:p>","DOI":"10.3390\/biom16040607","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:37:42Z","timestamp":1776677862000},"page":"607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["APOC3 Promotes DGAT2-Dependent Triglyceride Accumulation in Hepatocytes During Early Metabolic Dysfunction"],"prefix":"10.3390","volume":"16","author":[{"given":"Thi Nhi","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Min","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junho","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Research, Dongsan Medical Center, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9534-4329","authenticated-orcid":false,"given":"Eun Young","family":"Ha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0712-7728","authenticated-orcid":false,"given":"Hochan","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-5977","authenticated-orcid":false,"given":"Jae-Hyung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Keimyung University, Daegu 42601, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/j.jhep.2023.06.003","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"79","author":"Rinella","year":"2023","journal-title":"J. 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