Essential phospholipids impact cytokine secretion and alter lipid-metabolizing enzymes in human hepatocyte cell lines

Pharmacol Rep. 2024 Jun;76(3):572-584. doi: 10.1007/s43440-024-00595-4. Epub 2024 Apr 26.

Abstract

Background: Essential phospholipids (EPL) are hepatoprotective.

Methods: The effects on interleukin (IL)-6 and -8 secretion and on certain lipid-metabolizing enzymes of non-cytotoxic concentrations of EPL (0.1 and 0.25 mg/ml), polyenylphosphatidylcholine (PPC), and phosphatidylinositol (PtdIns) (both at 0.1 and 1 mg/ml), compared with untreated controls, were assessed in human hepatocyte cell lines (HepG2, HepaRG, and steatotic HepaRG).

Results: Lipopolysaccharide (LPS)-induced IL-6 secretion was significantly decreased in HepaRG cells by most phospholipids, and significantly increased in steatotic HepaRG cells with at least one concentration of EPL and PtdIns. LPS-induced IL-8 secretion was significantly increased in HepaRG and steatotic HepaRG cells with all phospholipids. All phospholipids significantly decreased amounts of fatty acid synthase in steatotic HepaRG cells and the amounts of acyl-CoA oxidase in HepaRG cells. Amounts of lecithin cholesterol acyltransferase were significantly decreased in HepG2 and HepaRG cells by most phospholipids, and significantly increased with 0.1 mg/ml PPC (HepaRG cells) and 1 mg/ml PtdIns (steatotic HepaRG cells). Glucose-6-phosphate dehydrogenase activity was unaffected by any phospholipid in any cell line.

Conclusions: EPL, PPC, and PtdIns impacted the secretion of pro-inflammatory cytokines and affected amounts of several key lipid-metabolizing enzymes in human hepatocyte cell lines. Such changes may help liver function improvement, and provide further insights into the EPL's mechanism of action.

Keywords: Essential phospholipids; HepG2; HepaRG; Non-alcoholic fatty liver disease; Steatotic HepaRG.

MeSH terms

  • Cell Line
  • Cytokines / metabolism
  • Hep G2 Cells
  • Hepatocytes* / drug effects
  • Hepatocytes* / metabolism
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Lipid Metabolism* / drug effects
  • Lipopolysaccharides / pharmacology
  • Phospholipids* / metabolism

Substances

  • Phospholipids
  • Lipopolysaccharides
  • Cytokines
  • Interleukin-6
  • Interleukin-8

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