Phospholipase A2 regulation of lipid droplet formation

Abstract

The classical regard of lipid droplets as mere static energy-storage organelles has evolved dramatically. Nowadays these organelles are known to participate in key processes of cell homeostasis, and their abnormal regulation is linked to several disorders including metabolic diseases (diabetes, obesity, atherosclerosis or hepatic steatosis), inflammatory responses in leukocytes, cancer development and neurodegenerative diseases. Hence, the importance of unraveling the cell mechanisms controlling lipid droplet biosynthesis, homeostasis and degradation seems evident Phospholipase A2s, a family of enzymes whose common feature is to hydrolyze the fatty acid present at the sn-2 position of phospholipids, play pivotal roles in cell signaling and inflammation. These enzymes have recently emerged as key regulators of lipid droplet homeostasis, regulating their formation at different levels. This review summarizes recent results on the roles that various phospholipase A2 forms play in the regulation of lipid droplet biogenesis under different conditions. These roles expand the already wide range of functions that these enzymes play in cell physiology and pathophysiology.

A snake venom group IIA PLA2 with immunomodulatory activity induces formation of lipid droplets containing 15-d-PGJ2 in macrophages

“…Our finding that inhibition of iPLA 2 by BEL and FKGK11 reduced CB-induced LD biogenesis indicates that this intracellular PLA 2 contributes to the effect of CB. However, although cPLA 2 has been reported to be relevant to LDs formation induced by diverse PAMPS stimuli and a snake venom inflammatory sPLA 2 25, 47 this intracellular PLA 2 does not participate in the genesis of LDs induced by CB in macrophages. A recent study showed the important role of iPLA 2 in fatty acid metabolism and triacylglycerol formation 62 .…”

“…Recently, the inflammatory group IIA sPLA 2 s have emerged as critical regulators of LD formation, as they provide free fatty acids from membrane phospholipids that are crucial for this process, directly regulating assembly of these organelles 25 . In light of this and the fact that CB, a group IIA sPLA 2 , is able to release arachidonic acid 7 , a major fatty acid involved in both LD formation and lipid-mediator production 26, 27 during inflammatory processes, we decided to investigate the ability of CB to induce LD formation and the mechanisms involved in LD formation, as well as 15-d-PGJ 2 production, in macrophages.…”

Group V Secreted Phospholipase A2 Is Upregulated by IL-4 in Human Macrophages and Mediates Phagocytosis via Hydrolysis of Ethanolamine Phospholipids

“…In summary, we provide novel data to indicate that sPLA 2 -V is required for efficient phagocytosis of zymosan particles and bacteria by IL-4-treated human macrophages and offer evidence that this requirement may involve generation of LPE, likely at the plasma membrane. In addition to its multiple roles in innate immunity and inflammation, sPLA 2 -V was suggested to participate in the progression of atherosclerosis (84). sPLA 2 -V-modified lowdensity lipoproteins promote foam cell formation, and the enzyme has been found in human atherosclerotic lesions.…”

Lipid droplets in leukocytes: Organelles linked to inflammatory responses

“…The first step in eicosanoid generation within any cell type is performed by a superfamily of enzymes collectively known as phospholipase (PL)A 2 due to their ability to release fatty acids from sn-2 position of phospholipids [36]. These enzymes are considered key regulators of LD homeostasis, regulating their formation at different levels [36].…”

“…The first step in eicosanoid generation within any cell type is performed by a superfamily of enzymes collectively known as phospholipase (PL)A 2 due to their ability to release fatty acids from sn-2 position of phospholipids [36]. These enzymes are considered key regulators of LD homeostasis, regulating their formation at different levels [36]. Under stimulation, cytosolic phospholipase A 2 (cPLA 2 ) co-localize with LDs from U937 cells [37] and dendritic cells, the resident macrophage population of the central nervous system [38] in parallel to increased LD formation.…”