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

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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.