Gene Deletion of Calcium-Independent Phospholipase A2γ (iPLA2γ) Suppresses Adipogenic Differentiation of Mouse Embryonic Fibroblasts

Biol Pharm Bull. 2020;43(9):1375-1381. doi: 10.1248/bpb.b20-00321.

Abstract

Adipogenic differentiation is a complex process by which fibroblast-like undifferentiated cells are converted into cells that accumulate lipid droplets. We here investigated the effect of gene deletion of calcium-independent phospholipase A2γ (iPLA2γ), a membrane-bound PLA2 enzyme, on adipogenic differentiation in mice. Since iPLA2γ knockout (KO) mice showed reduced fat volume and weight, we prepared mouse embryonic fibroblasts (MEF) from wild-type (WT) and iPLA2γ KO mice and examined the effect of iPLA2γ deletion on in vitro adipogenic differentiation. iPLA2γ increased during adipogenic differentiation in WT mouse-derived MEFs, and the differentiation was partially abolished in iPLA2γ KO-derived MEFs. In KO-derived MEFs, the inductions of peroxisome proliferator activator receptor γ (PPARγ) and CAAT/enhancer-binding protein α (C/EBPα) were also reduced during adipogenic differentiation, and the reductions in PPARγ and C/EBPα expressions and the defect in adipogenesis were restored by treatment with troglitazone, a PPARγ ligand. These results indicate that iPLA2γ might play a critical role in adipogenic differentiation by regulating PPARγ expression.

Keywords: adipogenesis; adipose differentiation; peroxisome proliferator activator receptor γ; phospholipase A2.

MeSH terms

  • Adipogenesis / drug effects
  • Adipogenesis / physiology*
  • Animals
  • CCAAT-Enhancer-Binding Proteins
  • Cell Differentiation / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Group VI Phospholipases A2 / genetics
  • Group VI Phospholipases A2 / metabolism*
  • Lysophospholipase / genetics
  • Lysophospholipase / metabolism*
  • Mice
  • Mice, Knockout
  • PPAR gamma / metabolism*
  • Primary Cell Culture
  • Troglitazone / pharmacology

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, mouse
  • PPAR gamma
  • Pparg protein, mouse
  • Group VI Phospholipases A2
  • Pla2g6 protein, mouse
  • Lysophospholipase
  • Troglitazone