Group X Secreted Phospholipase A2 Releases ω3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility

J Biol Chem. 2016 Mar 25;291(13):6895-911. doi: 10.1074/jbc.M116.715672. Epub 2016 Jan 31.


Within the secreted phospholipase A2(sPLA2) family, group X sPLA2(sPLA2-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid, a precursor of pro-inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA2-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free ω3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies usingPla2g10-deficient mice revealed that endogenous sPLA2-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized ω3 PUFAs or their metabolites to protect against dextran sulfate-induced colitis and to promote fertilization, respectively. In colitis, sPLA2-X deficiency increased colorectal expression of Th17 cytokines, and ω3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A2(cPLA2α) protects from colitis by mobilizing ω6 arachidonic acid metabolites, including prostaglandin E2 Thus, our results underscore a previously unrecognized role of sPLA2-X as an ω3 PUFA mobilizerin vivo, segregated mobilization of ω3 and ω6 PUFA metabolites by sPLA2-X and cPLA2α, respectively, in protection against colitis, and the novel role of a particular sPLA2-X-driven PUFA in fertilization.

Keywords: Phospholipase A; arachidonic acid (AA) (ARA); colitis; inflammation; lipid metabolism; membrane; polyunsaturated fatty acid (PUFA); prostaglandin; sperm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / antagonists & inhibitors
  • Arachidonic Acid / biosynthesis
  • Colitis / chemically induced
  • Colitis / enzymology
  • Colitis / genetics*
  • Colitis / therapy
  • Colon / enzymology*
  • Colon / pathology
  • Dextran Sulfate
  • Fatty Acids, Omega-3 / biosynthesis*
  • Fatty Acids, Omega-3 / metabolism
  • Fatty Acids, Omega-6 / biosynthesis
  • Fatty Acids, Omega-6 / metabolism
  • Fertility / genetics*
  • Gene Expression
  • Gene Expression Profiling
  • Group X Phospholipases A2 / genetics*
  • Group X Phospholipases A2 / metabolism
  • Humans
  • Interleukin-17 / biosynthesis
  • Male
  • Mice
  • Mice, Transgenic
  • Phospholipases A2 / genetics
  • Phospholipases A2 / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Sperm Count
  • Sperm Motility
  • Spermatozoa / enzymology*
  • Spermatozoa / pathology
  • Th17 Cells / metabolism
  • Th17 Cells / pathology
  • Transgenes


  • FFAR4 protein, mouse
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Interleukin-17
  • Receptors, G-Protein-Coupled
  • Arachidonic Acid
  • Dextran Sulfate
  • Group X Phospholipases A2
  • PLA2G10 protein, human
  • Phospholipases A2