Lipid Droplets, Phospholipase A2, Arachidonic Acid, and Atherosclerosis

Abstract

Lipid droplets, classically regarded as static storage organelles, are currently considered as dynamic structures involved in key processes of lipid metabolism, cellular homeostasis and signaling. Studies on the inflammatory state of atherosclerotic plaques suggest that circulating monocytes interact with products released by endothelial cells and may acquire a foamy phenotype before crossing the endothelial barrier and differentiating into macrophages. One such compound released in significant amounts into the bloodstream is arachidonic acid, the common precursor of eicosanoids, and a potent inducer of neutral lipid synthesis and lipid droplet formation in circulating monocytes. Members of the family of phospholipase A2, which hydrolyze the fatty acid present at the sn-2 position of phospholipids, have recently emerged as key controllers of lipid droplet homeostasis, regulating their formation and the availability of fatty acids for lipid mediator production. In this paper we discuss recent findings related to lipid droplet dynamics in immune cells and the ways these organelles are involved in regulating arachidonic acid availability and metabolism in the context of atherosclerosis.

Lipid Metabolism in Glioblastoma: From De Novo Synthesis to Storage

“…The most predominant features of LDs are their heterogeneity and diversity. The number, size, and composition of LDs vary widely between cells or even within the same cell depending on different conditions [ 109 , 112 , 129 , 130 , 131 ]. Only one LD with a diameter often >100 µm is found in most adipocytes, whereas a greater number of LDs are found in non-adipocyte cells and are usually <1 µm in diameter [ 132 , 133 ].…”

Roles of Palmitoleic Acid and Its Positional Isomers, Hypogeic and Sapienic Acids, in Inflammation, Metabolic Diseases and Cancer

“…In atherosclerosis lesions, activated endothelial cells release proinflammatory mediators that promote the transformation of the recruited monocytes into foam cells prior to their extravasation and further differentiation to foam macrophages in the intima [ 73 , 74 , 75 ]. Studies of the inflammatory state in early atherosclerotic plaques have shown that arachidonic acid is released in significant amounts to the bloodstream.…”

“…Studies of the inflammatory state in early atherosclerotic plaques have shown that arachidonic acid is released in significant amounts to the bloodstream. Several processes contribute to this release, including endothelial cells interacting with modified lipoproteins, platelets recruited to the activated endothelium, and secreted phospholipase A 2 s acting in situ on circulating lipoproteins [ 75 , 76 , 77 , 78 ]. The released arachidonate contributes to lipid droplet formation in the circulating monocytes, thus favoring their transformation into foamy, pro-atherogenic monocytes [ 66 , 79 , 80 ].…”

“…These data are in agreement with oth studies which, in addition, indicated that the 16:1n-7 effects work through reduction endoplasmic reticulum stress and activation of the NLRP3 inflammasome [7 Interestingly, these effects of 16:1n-7 were not reproduced by its trans isomer, suggesti that the double bond configuration is critical for atheroprotection [72]. In atherosclerosis lesions, activated endothelial cells release proinflammatory mediators that promote the transformation of the recruited monocytes into foam cells prior to their extravasation and further differentiation to foam macrophages in the intima [73][74][75]. Studies of the inflammatory state in early atherosclerotic plaques have shown that arachidonic acid is released in significant amounts to the bloodstream.…”

Differential Mobilization of the Phospholipid and Triacylglycerol Pools of Arachidonic Acid in Murine Macrophages

“…It has been suggested that AA-containing TAG may represent an expandable pool that is used by the cells when the glycerophospholipid membrane pool is replete. In this manner, AA entry into TAG would protect the cells from the deleterious effects produced by high concentrations of the free fatty acid and, in turn, help regulate the level of free AA available for lipid mediator synthesis [ 39 , 40 ]. An intriguing possibility that follows from these observations is that the TAG pool could represent a repository of AA for eventual transfer to membrane phospholipids.…”