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DOI: 10.1055/s-0032-1330826
Phospholipase A2 controls the membrane fatty acid uptake complex in hepatocytes
The mechanism by which fatty acids are taken up, i.e. by hepatocytes, and how this is regulated is unclear. Uncontrolled fat accumulation within the liver leads to steatosis and steaotohepatitis which are serious threats to health in Western populations. Here we show that fatty acid influx is mediated by a four-protein complex within specialized raft plasma membrane structures with phospholipase A2 (PLA2) serving as central regulator. Inhibition of PLA2 leads on the one hand to disintegration of the transport complex and at the same time to blockage of transporter biosynthesis by low lysophosphatidylcholine (LPC) formation. Low LPC suppresses JNK1 activation and, thus, fatty acid influx and lipapoptosis.
This newly discovered metabolic principle opens the door for therapeutic intervention of a yet untreatable disease. A perfect example of such a novel therapeutic strategy is the nontoxic bile acid-phospholipid conjugate UDCA-LPE which can reverse steatohepatitis by PLA2 inhibition, shown in mice models.