Group X secretory phospholipase a₂ negatively regulates adipogenesis in murine models

Studies in vitro indicate that group X secretory phospholipase A ₂ (GX sPLA₂) potently releases arachidonic acid (AA) and lysophosphatidylcholine from mammalian cell membranes. To define the function of GX sPLA₂ in vivo, our laboratory recently generated C57BL/6 mice with targeted deletion of GX sPLA₂ (GX^-/- mice). When fed a normal rodent diet, GX_-/- mice gained significantly more weight and had increased adiposity compared to GX^+/+ mice, which was not attributable to alterations in food consumption or energy expenditure. When treated with adipogenic stimuli ex vivo, stromal vascular cells isolated from adipose tissue of GX^-/- mice accumulated significantly more (20%) triglyceride compared to cells from GX^+/+ mice. Conversely, overexpression of GX sPLA₂, but not catalytically inactive GX sPLA₂, resulted in a significant 50% reduction in triglyceride accumulation in OP9 adipocytes. The induction of genes encoding adipogenic proteins (PPARγ, SREBP-1c, SCD1, and FAS) was also significantly blunted by 50-80% in OP9 cells overexpressing GX sPLA₂. Activation of the liver X receptor (LXR), a nuclear receptor known to up-regulate adipogenic gene expression, was suppressed in 3T3-L1 and OP9 cells when GX sPLA₂ was overexpressed. Thus, hydrolytic products generated by GX sPLA₂ negatively regulate adipogenesis, possibly by suppressing LXR activation.