New paradigm for secreted phospholipase A2 to control lipid metabolism and obesity.

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Metabolic disorders including obesity and insulin resistance have their basis on dysregulated lipid metabolism and low-grade inflammation. In a microarray search of unique lipase-related genes whose expressions are associated with obesity, we found that two secreted phospholipase A_2 (sPLA_2) enzymes, PLA2G5 and PLA2G2E, were robustly induced in adipocytes of obese mice. Analyses of Pla2g5^<-/-> and Pla2g2e^<-/-> mice revealed distinct and previously unrecognized roles of these sPLA_2s in diet-induced obesity. PLA2G5 protects from obesity-associated metabolic disorders by normalizing phosphatidylcholine in fat-overladen low-density lipoprotein and by tipping the immune balance toward a Th2-M2 state that counteracts adipose tissue inflammation. Collectively, the identification of “metabolic sPLA_2s” adds this gene family to a growing list of lipolytic enzymes that act as metabolic coordinators.