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

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 calciumindependent phospholipase A 2 γ (iPLA 2 γ), a membrane-bound PLA 2 enzyme, on adipogenic differentiation in mice. Since iPLA 2 γ knockout (KO) mice showed reduced fat volume and weight, we prepared mouse embryonic fibroblasts (MEF) from wild-type (WT) and iPLA 2 γ KO mice and examined the effect of iPLA 2 γ deletion on in vitro adipogenic differentiation. iPLA 2 γ increased during adipogenic differentiation in WT mousederived MEFs, and the differentiation was partially abolished in iPLA 2 γ 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 iPLA 2 γ might play a critical role in adipogenic differentiation by regulating PPARγ expression.

Systematic Review and Meta-Analysis of SERPINE1 4G/5G Insertion/Deletion Variant With Circulating Lipid Levels

“…Several underlying mechanisms could be proposed to explain the effects of the rs1799889 variant on lipids levels. (1) By repressing peroxisome proliferator-activated receptor γ (PPARγ) expression: PPARγ, a known adipogenic gene ( 20 ), plays a major role in TG synthesis ( 21 ), the inhibition of PAI-1 activity caused by rs1799889 ( 1 , 2 ) may repress the expression of PPARγ ( 3 ). As a result, the synthesis of TG was reduced; accordingly, the plasma levels of TG were decreased ( Tables 1 , 2 ).…”

“…The SERPINE1 gene is located on the long arm of human chromosome 7 (7q21. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. The most-studied rs1799889 variant, also known as 4G/5G insertion/deletion sequence, is located in the SERPINE1 promoter region and formed by the 5th guanine (G base) insertion or deletion in the 4G sequence at position-675th base.…”