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

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

doi:10.3390/nu15010040

journal article Open Access Dec 21, 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

Zoë J. Huggett Alison Smith

Nicola De Vivo Dhanny Gomez Preeti Jethwa John M. Brameld

Andrew Bennett

Andrew M. Salter

Nutrients Vol. 15 No. 1 pp. 40 · MDPI AG

View at Publisher Save 10.3390/nu15010040

Abstract

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.

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Details

Published: Dec 21, 2022
Vol/Issue: 15(1)
Pages: 40
License: View

Authors

Z

Zoë J. Huggett

Division of Food, Nutrition and Dietetics, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK; Fund for the Replacement of Animals in Medical Experiments (FRAME) Laboratory, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, Nottinghamshire, UK

A

Alison Smith

Division of Food, Nutrition and Dietetics, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK

N

Nicola De Vivo

Fund for the Replacement of Animals in Medical Experiments (FRAME) Laboratory, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, Nottinghamshire, UK

D

Dhanny Gomez

Fund for the Replacement of Animals in Medical Experiments (FRAME) Laboratory, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, Nottinghamshire, UK; National Institute for Health and Care Research (NIHR), Nottingham Biomedical Research Centre, Nottingham NG7 2UH, Nottinghamshire, UK

P

Preeti Jethwa

Division of Food, Nutrition and Dietetics, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK

J

John M. Brameld

Division of Food, Nutrition and Dietetics, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK

A

Andrew Bennett

Fund for the Replacement of Animals in Medical Experiments (FRAME) Laboratory, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, Nottinghamshire, UK; National Institute for Health and Care Research (NIHR), Nottingham Biomedical Research Centre, Nottingham NG7 2UH, Nottinghamshire, UK

A

Andrew M. Salter

Division of Food, Nutrition and Dietetics, School of Biosciences, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK; Future Food Beacon, Sutton Bonington Campus, University of Nottingham, Loughborough LE12 5RD, Leicestershire, UK

Funding

Rank Prize Fund

Cite This Article

Zoë J. Huggett, Alison Smith, Nicola De Vivo, et al. (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), 40. https://doi.org/10.3390/nu15010040

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

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