Lipid Droplet Biogenesis Induced by Stress Involves Triacylglycerol Synthesis That Depends on Group VIA Phospholipase A2

Abstract

This work investigates the metabolic origin of triacylglycerol (TAG) formed during lipid droplet (LD) biogenesis induced by stress. Cytotoxic inhibitors of fatty acid synthase induced TAG synthesis and LD biogenesis in CHO-K1 cells, in the absence of external sources of fatty acids. TAG synthesis was required for LD biogenesis and was sensitive to inhibition and down-regulation of the expression of group VIA phospholipase A 2 (iPLA 2 -VIA). Induction of stress with acidic pH, C 2 -ceramide, tunicamycin, or deprivation of glucose also stimulated TAG synthesis and LD formation in a manner dependent on iPLA 2 -VIA. Overexpression of the enzyme enhanced TAG synthesis from endogenous fatty acids and LD occurrence. During stress, LD biogenesis but not TAG synthesis required phosphorylation and activation of group IVA PLA 2 (cPLA 2 ␣). The results demonstrate that iPLA 2 -VIA provides fatty acids for TAG synthesis while cPLA 2 ␣ allows LD biogenesis. LD biogenesis during stress may be a survival strategy, recycling structural phospholipids into energy-generating substrates.

Lipid Droplets: Their Role in Nanoparticle-Induced Oxidative Stress

“…[43][44][45][46] Recently, Gubern et al demonstrated that triglyceride synthesis and LD biogenesis during stress mainly takes place from pre-existing fatty acids and is dependent on group VI phospholipase A 2 (PLA 2 -VIA). 40 One possible explanation for LD accumulation is the impairment in mitochondrial fatty acid -oxidation, resulting from mitochondrial membrane damage, and leading to an increase in triglyceride storage. 14, 47,48 Results from our studies suggest that assessment of LD accumulation may serve as a biological marker of oxidative stress and indicate disrupted lipid homeostasis by nanomaterials.…”

JNK and Ceramide Kinase Govern the Biogenesis of Lipid Droplets through Activation of Group IVA Phospholipase A2

“…Cells generate LD from exogenous sources, free fatty acids or lipoproteins, but LD also appear in the absence of external lipids when cells are under stress, apparently after the recycling of membrane phospholipids into TAG (7). We have shown recently that group IVA PLA 2 (also termed cPLA 2 ␣) is required for LD biogenesis either after exogenous lipid loading (10) or during stress (7).…”

“…We have shown recently that group IVA PLA 2 (also termed cPLA 2 ␣) is required for LD biogenesis either after exogenous lipid loading (10) or during stress (7). Regardless of the LD-inducing situation, the enzyme is not involved in the synthesis of neutral lipids; rather, it allows the formation of LD from TAG-containing membranes.…”

“…In the last few years, the biology of LD has received increasing interest, due to the close relationship between an excess of lipid storage in certain tissues and pathologies such as obesity, diabetes, or atherosclerosis (3)(4)(5). Cellular stress has been related to the generation of LD, which might play a cytoprotective role (6,7). Therefore, dissecting the signaling pathways leading to LD formation may have important clinical applications in metabolic diseases and also in neurodegenerative diseases such as Parkinson and Alzheimer disease (8,9).…”

Not Just Fat: The Structure and Function of the Lipid Droplet

“…Unsaturated fatty acids help cells to circumvent the toxicity of saturated fatty acid in mammalian cells by promoting TG production (Listenberger et al 2003). This function is also important in cardiomyocytes that are exposed to ischemia and reperfusion (Barba et al 2009), neurons during nutrient deprivation (Du et al (Gubern et al 2009). In Saccharomyces cerevisiae, a mutant lacking all lipid ester synthesis is viable under the normal conditions (Sandager et al 2002), but excess unsaturated fatty acids causes massive membrane proliferation and cell death ).…”