Group X secretory phospholipase a2 negatively regulates adipogenesis in murine models

Xia Li, Preetha Shridas, Kathy Forrest, William Bailey, Nancy R. Webb

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Studies in vitro indicate that group X secretory phospholipase A 2 (GX sPLA2) potently releases arachidonic acid (AA) and lysophosphatidylcholine from mammalian cell membranes. To define the function of GX sPLA2 in vivo, our laboratory recently generated C57BL/6 mice with targeted deletion of GX sPLA2 (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 sPLA2, but not catalytically inactive GX sPLA2, 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 sPLA2. 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 sPLA2 was overexpressed. Thus, hydrolytic products generated by GX sPLA2 negatively regulate adipogenesis, possibly by suppressing LXR activation.

Original languageEnglish
Pages (from-to)4313-4324
Number of pages12
JournalFASEB Journal
Volume24
Issue number11
DOIs
StatePublished - Nov 2010

Keywords

  • Arachidonic acid
  • Nuclear receptor
  • Obesity

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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