Metabolic regulation by secreted phospholipase A₂

Within the phospholipase A₂ (PLA₂) superfamily that hydrolyzes phospholipids to yield fatty acids and lysophospholipids, the secreted PLA₂ (sPLA₂) enzymes comprise the largest family that contains 11 isoforms in mammals. Individual sPLA₂s exhibit unique distributions and specific enzymatic properties, suggesting their distinct biological roles. While sPLA₂s have long been implicated in inflammation and atherosclerosis, it has become evident that they are involved in diverse biological events through lipid mediator-dependent or mediator-independent processes in a given microenvironment. In recent years, new biological aspects of sPLA₂s have been revealed using their transgenic and knockout mouse models in combination with mass spectrometric lipidomics to unveil their target substrates and products in vivo. In this review, we summarize our current knowledge of the roles of sPLA₂s in metabolic disorders including obesity, hepatic steatosis, diabetes, insulin resistance, and adipose tissue inflammation.