Lysophosphatidylcholine (LPC) as central player for control of hepatocellular fatty acid influx

Background: In NASH the intracellular ratio of phosphatidylcholine (PC): lysophosphatidylcholine (LPC) is decreased due to activation of phospholipase A2. Responsible is the calcium independent membrane phospholipase A2 (iPLA2β) which is part of the heterotetrameric fatty acid uptake complex consisting also of FABPPM, CD36 and caveolin1. The bile acid-phospholipid conjugate UDCA-LPE inhibits fatty acid influx by interference with iPLA2β.

Aim: Evaluation of the metabolic consequences of iPLA2β inhibition by UDCA-LPE in HepG2 cells.

Methods: In HepG2 cells the bile acid-phospholipid conjugate ursodeoxycholate-lysophosphatidylethanolamide (UDCA-LPE) as iPLA2β inhibitor was used to modify intracellular LPC levels. We examined the impact of LPC on p-JNK1 and transcription of the heterotetrameric fatty acid transport complex constituted of CD36, FABPPM, caveolin1 and iPLA2β.

Results: Inhibition of iPLA2β by UDCA-LPE resulted in suppression of cytosolic lysophosphatidylcholine (LPC) which was accompanied by a corresponding decrease of phosphorylated JNK1. Low pJNK1 suppressed the synthesis of all four members of the fatty acid uptake complex. Thus, the complex faded from the detergent resistant plasma membrane fraction explaining the inhibition of fatty acid influx in hepatocytes. The role of LPC as inducer of pJNK1 was supported by in vitro addition of 1 – 10µM LPC to delipidated cytosolic extracts. It resulted in pJNK1 dependent synthesis stimulation of the fatty acid uptake complex.

Conclusion: The generation of LPC controls via JNK1 the constitution of the membrane fatty acid uptake complex.

Corresponding author: Stremmel, Wolfgang

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