{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:59:04Z","timestamp":1790686744267,"version":"4.1.0"},"reference-count":27,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation (NRF) funded by the Korean Government","doi-asserted-by":"publisher","award":["RS-2022-NR068424"],"award-info":[{"award-number":["RS-2022-NR068424"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003716","name":"Korea Basic Science Institute","doi-asserted-by":"publisher","award":["C623200"],"award-info":[{"award-number":["C623200"]}],"id":[{"id":"10.13039\/501100003716","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003716","name":"Korea Basic Science Institute","doi-asserted-by":"publisher","award":["C612101"],"award-info":[{"award-number":["C612101"]}],"id":[{"id":"10.13039\/501100003716","id-type":"DOI","asserted-by":"publisher"}]},{"award":["C623200"],"award-info":[{"award-number":["C623200"]}],"id":[{"id":"https:\/\/ror.org\/0417sdw47","id-type":"ROR","asserted-by":"publisher"}]},{"award":["C612101"],"award-info":[{"award-number":["C612101"]}],"id":[{"id":"https:\/\/ror.org\/0417sdw47","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by hepatic steatosis, metabolic stress, and inflammation. Although free fatty acid (FFA)-based in vitro models are widely used, how OA:PA ratios shape hepatocellular phenotypes remains incompletely characterized. HepG2 cells were treated with oleic acid (OA), palmitic acid (PA), or four OA:PA mixtures (O1P1, O2P1, O3P2, O1P2) for 24 or 48 h. OA and OA:PA mixtures were evaluated at 500 \u03bcM total FFA (O2P1: 333.3 \u03bcM OA + 166.7 \u03bcM PA; O3P2: 300 \u03bcM OA + 200 \u03bcM PA), whereas PA alone was evaluated at 200 \u03bcM. Cell viability, lipid accumulation, ultrastructure, oxidative response, secreted cytokines, and molecular responses were evaluated. Distinct OA:PA ratios generated discrete hepatocellular states rather than a linear steatosis-to-lipotoxicity continuum. O3P2 produced a steatosis-dominant phenotype with pronounced lipid accumulation and relatively limited stress signaling. In contrast, O2P1 combined substantial lipid accumulation with elevated DCF fluorescence, AMP-activated protein kinase (AMPK) phosphorylation, nuclear factor kappa B (NF-\u03baB)-associated inflammatory signaling, and interleukin-8 (IL-8) secretion, representing a pronounced stress-responsive phenotype with selected MASH-relevant features. Selected responses were also evaluated in SNU-449 cells, revealing cell-line-specific patterns. Collectively, these findings support a phenotype-oriented framework for OA:PA ratio selection in hepatocyte-based in vitro MASH modeling.<\/jats:p>","DOI":"10.3390\/cells15191774","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:09:25Z","timestamp":1790683765000},"page":"1774","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct OA:PA Ratios Generate Discrete Hepatocellular Phenotypes in HepG2 Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5429-9181","authenticated-orcid":false,"given":"Hangyeon","family":"Jeong","sequence":"first","affiliation":[{"name":"Center for Bio-Imaging & Translational Research, Korea Basic Science Institute, Cheongju 28119, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yesol","family":"Han","sequence":"additional","affiliation":[{"name":"Center for Bio-Imaging & Translational Research, Korea Basic Science Institute, Cheongju 28119, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2207-2189","authenticated-orcid":false,"given":"Jiyeong","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Bio-Imaging & Translational Research, Korea Basic Science Institute, Cheongju 28119, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Hanbyul","family":"Noh","sequence":"additional","affiliation":[{"name":"Center for Bio-Imaging & Translational Research, Korea Basic Science Institute, Cheongju 28119, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6632-8071","authenticated-orcid":false,"given":"Eunyoung","family":"Moon","sequence":"additional","affiliation":[{"name":"Center for Bio-Imaging & Translational Research, Korea Basic Science Institute, Cheongju 28119, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Yanghoon","family":"Huh","sequence":"additional","affiliation":[{"name":"Center for Bio-Imaging & Translational Research, Korea Basic Science Institute, Cheongju 28119, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,29]]},"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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