Essential phospholipids decrease apoptosis and increase membrane transport in human hepatocyte cell lines

• Published in: Lipids in health and disease Vol. 21; no. 1; pp. 1 - 91
• Main Authors: Wupperfeld, Dominik, Fricker, Gert, Bois De Fer, Béatrice, Frank, Larissa, Wehrle, Annika, Popovic, Branko
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 24-09-2022; BioMed Central; BMC
• Subjects: Apoptosis; Bile; Biological transport; Breast cancer; Cell culture; Cytotoxicity; Enzymes; Fluidity; Gene expression; Health aspects; HepaRG; Hepatitis; HepG2; Lipids; Liver cells; Liver diseases; Membrane fluidity; Mortality; Multidrug resistance; Nonalcoholic fatty liver disease; P-Glycoprotein; Phosphatidylinositol; Phospholipids; Protein transport; Proteins; Steatotic HepaRG; Germany; United States > US
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-022-01698-8

Background Essential phospholipids (EPL) have hepatoprotective effects across many liver diseases/conditions. The impact of EPL on hepatocyte function in vitro was investigated. Methods Effects of noncytotoxic concentrations of EPL (0.1 and 0.25 mg/ml), and its constituents, polyenylphosphatidylcholine (PPC) and phosphatidylinositol (PI) (both at 0.1 and 1 mg/ml), on membrane fluidity, apoptosis and extracellular transport versus controls were investigated in human hepatocyte cell lines (HepG2, HepaRG, steatotic HepaRG). Results Significantly increased membrane fluidity occurred with all 3 phospholipids (PLs) in HepG2 cultures, and with PI (1 mg/ml) in steatotic HepaRG cells. Significantly decreased tamoxifen-induced apoptosis was observed in HepG2 cells with EPL, PPC and PI. Breast cancer resistance protein (BCRP) activity was significantly increased by EPL and PI in HepG2 cells. Multidrug resistance-associated protein 2 (MRP-2) activity was unaffected by any PL in HepG2 cells, and significantly increased by EPL, PI and PPC (1 mg/ml) in HepaRG cells, and by PI (1 mg/ml) in steatotic HepaRG cells. Bile salt export protein (BSEP) activity in HepG2 cells and steatotic HepaRG cells was significantly increased by EPL (0.25 mg/ml), and PPC (both concentrations), but not by PI. The PLs had no effects on HepaRG cell BSEP activity. P-glycoprotein (P-GP) activity was significantly increased by all compounds in HepG2 cells. PI (1 mg/ml) significantly increased P-GP activity in HepaRG and steatotic HepaRG cells. Conclusions EPL, PPC, and PI increased hepatocyte membrane fluidity, decreased apoptosis and increased hepatocellular export, all of which may improve liver function. These in-vitro investigations provide valuable insights into the mechanism of action of EPL. Keywords: HepG2, HepaRG, Steatotic HepaRG, Nonalcoholic fatty liver disease