Group X secretory phospholipase A 2 negatively regulates adipogenesis in murine models

Studies in vitro indicate that group X secretory phospholipase A 2 (GX sPLA 2 ) potently releases arachidonic acid (AA) and lysophosphatidylcholine from mammalian cell membranes. To define the function of GX sPLA 2 in vivo , our laboratory recently generated C57BL/6 mice with targeted deletion of GX sPLA 2 (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 sPLA 2 , but not catalytically inactive GX sPLA 2 , 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 sPLA 2 . 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 sPLA 2 was overexpressed. Thus, hydrolytic products generated by GX sPLA 2 negatively regulate adipogenesis, possibly by suppressing LXR activation.—Li, X., Shridas, P., Forrest, K., Bailey, W., Webb, N. R. Group X secretory phospholipase A 2 negatively regulates adipogenesis in murine models. FASEB J . 24, 4313–4324 (2010). www.fasebj.org