This family represents PNPLA3 (patatin-like phospholipase domain-containing protein 3) from mammals, also known as ADPN (adiponutrin) or iPLA2-epsilon (calcium-independent phospholipase A2). PNPLA3 is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes and is an indicator of the nutritional state. Human adiponutrins are bound to the cell membrane of adipocytes and show transacylase, TG hydrolase, and PLA2 activity [, , ]. In murine models, PNPLA3 was found to be involved in the hepatic metabolism of triglycerides and in the regulation of systemic glucose homeostasis [].
This entry includes patatin-like phospholipase domain-containing proteins 1-5 (PNPLA1-5) from humans and Atgl-1 from Caenorhabditis elegans. They are a group of lipid hydrolases. Atgl-1 may play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion [, , , , , ]. In humans PNPLA1 has a role in the formation of the epidermal lipid barrier; mutations in this gene are associated with the skin disorder known as ichthyosis []. PNPLA1 acts as an omega-hydroxyceramide transacylase involved in the synthesis of omega-O-acylceramides (esterified omega-hydroxyacyl-sphingosine; EOS), which are extremely hydrophobic lipids involved in skin barrier formation [, ]. It catalyzes the last step of the synthesis of omega-O-acylceramides by transferring linoleic acid from triglycerides to an omega-hydroxyceramid [].Human PNPLA2 catalyses the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets []. PNPLA3 has both triacylglycerol lipase and acylglycerol O-acyltransferase activities [].
