Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Effects of Fatty Acids, Fructose and Glucose on the Accumulation of Lipid in Liver Cells: A Comparison of Primary Human Hepatocytes and Hepatoma Cell Lines

Version 1 : Received: 28 November 2022 / Approved: 30 November 2022 / Online: 30 November 2022 (03:28:19 CET)

A peer-reviewed article of this Preprint also exists.

Huggett, Z.J.M.; Smith, A.J.; De Vivo, N.; Gomez, D.; Jethwa, P.; Brameld, J.M.; Bennett, A.M.; Salter, A.M. 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 2023, 15, 40. Huggett, Z.J.M.; Smith, A.J.; De Vivo, N.; Gomez, D.; Jethwa, P.; Brameld, J.M.; Bennett, A.M.; Salter, A.M. 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 2023, 15, 40.

Abstract

Abstract: Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We inves-tigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different hepatoma cell lines: HepG2, Huh7 and McA-RH7777 (McA). Cells were treated for 48 hours with fatty acids (0 or 200μM), glucose (5mM or 11mM) and fructose (0mM, 2mM or 8mM). 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 11mM glucose plus fatty acids (P=0.004, fatty acid x 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 x insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (P<0.001 insulin x 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.

Keywords

Non-alcoholic liver disease; fructose; glucose; steatosis; hepatocyte; hepatoma cells

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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