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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

Huggett, Zoë J.; Smith, Alison; De Vivo, Nicola; Gomez, Dhanny; Jethwa, Preeti; Brameld, John M.; Bennett, Andrew; Salter, Andrew M.


Zoë J. Huggett

Alison Smith

Nicola De Vivo

Dhanny Gomez

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Professor of Nutritional Biochemstry

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Professor of Nutritional Biochemistry


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–derived 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 μM), 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 < 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 × glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (p < 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 < 0.001 for fatty acid × insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (p < 0.001 insulin × 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.


Huggett, Z. J., Smith, A., De Vivo, N., Gomez, D., Jethwa, P., Brameld, J. M., …Salter, A. M. (2022). 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. Nutrients, 15(1), Article 40.

Journal Article Type Article
Acceptance Date Dec 19, 2022
Online Publication Date Dec 21, 2022
Publication Date Dec 21, 2022
Deposit Date Dec 24, 2022
Publicly Available Date Jan 6, 2023
Journal Nutrients
Electronic ISSN 2072-6643
Publisher MDPI
Peer Reviewed Peer Reviewed
Volume 15
Issue 1
Article Number 40
Keywords Food Science; Nutrition and Dietetics
Public URL
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