Abnormal lipid metabolism and disease caused by deficiency of atypical secretory phospholipase A2 (sPLA2-III)

我们已经证明，III组磷脂酶A2 （sPLA2-III）是分泌磷脂酶A2 （sPLA2）家族的一员，在小鼠近端附睾上皮中表达，并且靶向破坏编码该蛋白的基因（Pla2g3）导致精子成熟和生育缺陷。我们的研究结果揭示了非典型sPLA2家族成员sPLA2- iii在附睾脂质稳态中的作用，并表明其扰动可能导致精子功能障碍。此外，sPLA2-III在白色脂肪组织间质血管部分的前脂肪细胞中组成性表达。高脂饮食诱导的肥胖、脂肪性肝炎、高脂血症、高血糖和胰岛素抵抗均得到改善。与野生型小鼠相比，Pla2g3-/-小鼠脂肪或肝脏脂肪生成、脂肪生成和促炎基因的表达以及溶血磷脂酰胆碱的脂肪水平显著降低。

We have shown that group III phospholipase A2 (sPLA2-III), a member of the secreted phospholipase A2 (sPLA2) family, is expressed in the mouse proximal epididymal epithelium and that targeted disruption of the gene encoding this protein (Pla2g3) leads to defects in sperm maturation and fertility. Our results reveal a role for the atypical sPLA2 family member sPLA2-III in epididymal lipid homeostasis and indicate that its perturbation may lead to sperm dysfunction. Additionally, sPLA2-III was expressed constitutively in preadipocytic cells in the stromal vascular fraction of white adipose tissue. High-fat diet induced obesity, steatohepatitis, hyperlipidemia, hyperglycemia and insulin resistance were ameliorated in Pla2g3-/- mice. Adipose or hepatic expression of lipogenic, adipogenic and proinflammatory genes and adipose level of lysophosphatidylcholine were significantly reduced in Pla2g3-/- mice compared with wild-type mice.