{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:24:58Z","timestamp":1789021498924,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rank Prize Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We investigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different cell lines: HepG2 (human hepatoblastoma\u2013derived cell line), Huh7 (human hepatocellular carcinoma cell line) and McA-RH7777 (McA, rat hepatocellular carcinoma cell line). Cells were treated for 48 h with fatty acids (0 or 200 \u03bcM), glucose (5 mM or 11 mM) and fructose (0 mM, 2 mM or 8 mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (p &lt; 0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11 mM glucose plus fatty acids (p = 0.004, fatty acid \u00d7 glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (p &lt; 0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (p = 0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (p &lt; 0.001 for fatty acid \u00d7 insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (p &lt; 0.001 insulin \u00d7 cell type interaction). Hence, glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH.<\/jats:p>","DOI":"10.3390\/nu15010040","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T02:31:11Z","timestamp":1671676271000},"page":"40","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["A Comparison of Primary Human Hepatocytes and Hepatoma Cell Lines to Model the Effects of Fatty Acids, Fructose and Glucose on Liver Cell Lipid Accumulation"],"prefix":"10.3390","volume":"15","author":[{"given":"Zo\u00eb J.","family":"Huggett","sequence":"first","affiliation":[{"name":"Division of Food, Nutrition and Dietetics, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK"},{"name":"Fund for the Replacement of Animals in Medical Experiments (FRAME) Laboratory, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, Nottinghamshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Food, Nutrition and Dietetics, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"De Vivo","sequence":"additional","affiliation":[{"name":"Fund for the Replacement of Animals in Medical Experiments (FRAME) Laboratory, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, Nottinghamshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhanny","family":"Gomez","sequence":"additional","affiliation":[{"name":"Fund for the Replacement of Animals in Medical Experiments (FRAME) Laboratory, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, Nottinghamshire, UK"},{"name":"National Institute for Health and Care Research (NIHR), Nottingham Biomedical Research Centre, Nottingham NG7 2UH, Nottinghamshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preeti","family":"Jethwa","sequence":"additional","affiliation":[{"name":"Division of Food, Nutrition and Dietetics, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4942-080X","authenticated-orcid":false,"given":"John M.","family":"Brameld","sequence":"additional","affiliation":[{"name":"Division of Food, Nutrition and Dietetics, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Bennett","sequence":"additional","affiliation":[{"name":"Fund for the Replacement of Animals in Medical Experiments (FRAME) Laboratory, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, Nottinghamshire, UK"},{"name":"National Institute for Health and Care Research (NIHR), Nottingham Biomedical Research Centre, Nottingham NG7 2UH, Nottinghamshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8922-673X","authenticated-orcid":false,"given":"Andrew M.","family":"Salter","sequence":"additional","affiliation":[{"name":"Division of Food, Nutrition and Dietetics, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK"},{"name":"Future Food Beacon, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jhep.2018.10.033","article-title":"Non-alcoholic fatty liver disease\u2014A global public health perspective","volume":"70","author":"Younossi","year":"2019","journal-title":"J. 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