Abstract 3591: Group X sPLA2 Deficiency Increases Adiposity and Adipose Tissue Inflammation in Mice
Introduction: Of the 10 secretory phospholipase A2 (sPLA2) enzymes expressed in humans, Group X (GX) sPLA2 is the most potent in hydrolyzing phospholipids on cell membranes. In addition to its lipolytic activity, GX sPLA2 is also a high affinity ligand for the M-type sPLA2 receptor. Although numerous studies have implicated GX sPLA2 in important biological processes in vitro, data from studies in vivo are lacking. To elucidate the physiological functions of this enzyme we recently developed C57BL/6 mice with targeted deletion of the GX sPLA2 gene.
Results: Analysis by real time RT-PCR showed that GX sPLA2 mRNA is widely distributed in mouse tissues, with highest expression in intestine, testes, brain, thymus, spleen, fat, lung, and heart. Unlike some of the other members of the sPLA2 family, tissue expression of GX sPLA2 was not highly upregulated in mice injected with lipopolysaccharide. However, GX sPLA2 was induced almost 5-fold in retroperitoneal fat of mice fed a high-fat (60 kcal%) diet for 17 weeks.Targeted disruption of GX sPLA2 resulted in increased body weight in 1.5 year-old mice fed a normal laboratory diet (male GX sPLA2+/+ mice: 35.8±0.4 g; male GX sPLA2−/− mice: 45.033.2 g; p<0.05). The increase in body weight was associated with significantly increased percent body fat (GX sPLA2+/+ mice: 16.0±1.0%; GX sPLA2−/− mice: 19.6±1%; p<0.05), increased adipocyte size (GX sPLA2+/+ mice: 1300±26 um2 GX sPLA2 −/− mice: 2700±78 um2; p<0.001), and decreased fasting plasma triglyceride levels (GX sPLA2+/+ mice: 46.3±4.9 mg/dl; GX sPLA2−/− mice: 33.8±2.9 mg/dl; p<0.05) at 3 months of age. Food consumption, fasting blood glucose, and plasma total cholesterol levels were not significantly different between GX sPLA2−/− and GX sPLA2+/+ mice. Compared to 3 month old GX sPLA2+/+ mice, the relative expression of IL-6 and F4/80 mRNAs in adipose tissue of age-matched GX sPLA2−/− mice was increased 9- and 4-fold, respectively, suggesting that the increased adiposity in GX sPLA2−/− mice was associated with an increase in the inflammatory profile of adipose tissue
Conclusions: Our data points to a previously unrecognized role for Group X sPLA2 in the development of obesity and associated adipose tissue inflammation.