{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T14:34:37Z","timestamp":1789396477102,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"a University of Otago Division of Health Sciences Dean\u2019s Bequest Grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Metabolic (dysfunction)-associated steatotic liver disease (MASLD), the hepatic consequence of metabolic syndrome, affects 30% of the global population. Studies in animals and humans investigating the effect of fructose on MASLD present conflicting findings, while in vitro methods often fail to add meaningful evidence due to acute exposures (&lt;72 h) and non-physiological concentrations. This study aimed to determine the effect of fructose on triglyceride (TG) accumulation in HepG2 cells following acute and chronic exposures and assess its effect on the expression of genes related to de novo lipogenesis (DNL). Methods: TG concentration was measured after 48 h in response to fructose (20 mM) or glucose (20 mM), with or without a fatty acid mixture (oleic acid\/palmitic acid 110 \u00b5M\/55 \u00b5M), in low (5.5 mM)- and high (25.5 mM)-glucose media. To model chronic exposure, cells were maintained in fructose, glucose, or fatty acids for 28 days and the TG concentration was determined every 7 days. The effect of fructose on DNL regulators (SREBPF1, NR1H3, FASN, and ACACA) was determined using qPCR. Results: Neither fructose nor glucose, with or without fatty acids, changed the TG levels in cells at 48 h and the media glucose concentration had no effect on this result. Similarly, fructose did not increase TG levels after 28 days. While fructose and glucose did not affect key DNL genes at 6 h, the fatty acid mixture reduced FASN by 41%. Conclusions: This study shows that fructose did not significantly impact TG synthesis or DNL gene expression in the HepG2 cell model. Future studies should consider using primary human hepatocytes or more complex in vitro models.<\/jats:p>","DOI":"10.3390\/nu17172762","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T14:18:49Z","timestamp":1756217929000},"page":"2762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Fructose on Features of Steatotic Liver Disease in HepG2 Cells"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4654-2512","authenticated-orcid":false,"given":"Matthew Thomas","family":"Howes","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3468-3394","authenticated-orcid":false,"given":"Jessie","family":"King","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda Joy","family":"Rosengren","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Otago, Dunedin 9016, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101133","DOI":"10.1016\/j.aohep.2023.101133","article-title":"A Multi-Society Delphi Consensus Statement on New Fatty Liver Disease Nomenclature","volume":"29","author":"Rinella","year":"2023","journal-title":"Ann. 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