Reduced expression of adipose triglyceride lipase decreases arachidonic acid release and prostacyclin secretion in human aortic endothelial cells

Riederer, Monika; Lechleitner, Margarete; Köfeler, Harald; Frank, Saša

doi:10.1080/13813455.2017.1309052

Cited by 21 publications

(16 citation statements)

References 24 publications

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“…Recent evidence has suggested that TAG lipolysis mediated by ATGL contributes to the production of lipid mediators in endothelial and immune cells (Dichlberger et al , 2014; Schlager et al , 2015; Riederer et al , 2017). Here we asked whether lipid droplet breakdown via ATGL is required for lipid mediator production in serum-starved cancer cells, and whether it mediates hGX-sPLA 2 -stimulated PGE 2 synthesis.…”

Section: Resultsmentioning

confidence: 99%

“…In immune and cancer cells, LDs have long been implicated in AA storage, trafficking and eicosanoid production (Dvorak et al , 1983; Triggiani et al , 1994; Bozza et al , 2011). It was only recently shown that ATGL provides precursors for lipid mediator production and modulates neutrophil immune responses in vivo (Dichlberger et al , 2014; Schlager et al , 2015; Riederer et al , 2017). However, it is not yet clear how LDs manage PUFA trafficking for lipid mediator production in mammalian cells and how they cooperate with the canonical PLA 2 -mediated pathways (Guijas et al , 2014; Jarc & Petan, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Lipid droplets control mitogenic lipid mediator production in human cancer cells

Petan

Eichmann²,

Zimmermann³

et al. 2021

Preprint

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Lipid droplets are dynamic organelles with a central role in fatty acid metabolism. They protect cells from lipotoxicity by sequestering excess fatty acids but also provide fatty acids for metabolic reactions and signalling events. Here we show that lipid droplet turnover in cancer cells is required for production of ω-3 and ω-6 polyunsaturated fatty acid (PUFA)-derived inflammatory lipid mediators, including eicosanoids and specialised pro-resolving mediators. We show that incorporation of PUFAs into triglycerides mediated by diacylglycerol acyltransferase 1 (DGAT1), and their release by adipose triglyceride lipase (ATGL), are required for cyclooxygenase- and lipoxygenase-dependent lipid mediator production and cancer cell proliferation. The human group X secreted phospholipase A2 (hGX sPLA2) drives the delivery of membrane-derived PUFAs into lipid droplets, while ATGL promotes the incorporation of lipid droplet-derived PUFAs into phospholipids. The group IVA cytosolic PLA2 (cPLA2α) acts on membrane phospholipids and complements ATGL in the regulation of PUFA trafficking between phospholipids and triglycerides. This study identifies lipid droplets as essential cellular hubs that control PUFA availability for production of lipid mediators involved in inflammation and tumorigenesis.SynopsisThis study shows that lipid droplets in cancer cells control the supply of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) for the production of lipid mediators, which in turn drive cancer cell proliferation. The esterification of PUFAs into triacylglycerols (TAGs) and their release from lipid droplets are necessary for PUFA entry into lipid mediator production pathways. Lipid mediator production induced by the human group X secreted phospholipase A2 (hGX sPLA2), which releases PUFAs from the plasma membrane and serum lipoproteins, depends on diacylglycerol acyltransferase 1 (DGAT1)-mediated TAG synthesis.Adipose triglyceride lipase (ATGL) liberates ω-3 and ω-6 PUFAs from TAGs and drives lipid mediator production via cyclooxygenase (COX) and lipoxygenase (LOX) pathways.ATGL promotes the incorporation of lipid droplet-derived PUFAs into phospholipids, which are targeted by the group IVA cytosolic PLA2 (cPLA2α), thereby selectively supplying arachidonic acid for lipid mediator production.Lipid droplets are required for cPLA2α-induced lipid mediator production also in cells that do not depend on ATGL for the supply PUFAs into lipid mediator pathways.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lipid droplets control mitogenic lipid mediator production in human cancer cells

Petan

Eichmann²,

Zimmermann³

et al. 2021

Preprint

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“…Patients with high ARA levels at baseline showed a 54% increased probability of requiring surgical repair during follow-up. Previous research concentrated on aortic endothelial cells and aortic smooth muscle cells [ 62 , 63 ]. Despite the focus on aortic cells, there are very few studies about aortic dissection or aneurysm.…”

Section: Discussionmentioning

confidence: 99%

Serum Oxylipin Profiles Identify Potential Biomarkers in Patients with Acute Aortic Dissection

et al. 2022

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Aortic dissection (AD) is a life-threatening cardiovascular disease with a dismal prognosis. Inflammation plays an important role in AD. Oxylipins are bioactive lipids involved in the modulation of inflammation and may be involved in the pathogenesis and progression of AD. This study aims to identify possible metabolites related to AD. A total of 10 type A Aortic dissection (TAAD) patients, 10 type B Aortic dissection (TBAD) patients and 10 healthy controls were included in this study. Over 100 oxylipin species were identified and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. Our investigation demonstrated substantial alterations in 91 oxylipins between AD and healthy individuals. Patients with TAAD had 89 entries accessible compared to healthy controls. According to orthogonal partial least squares discriminant analysis (OPLS-DA), fitness (R2X = 0.362 and R2Y = 0.807, p = 0.03) and predictability (Q2 = 0.517, p = 0.005) are the validation parameters between the two groups. Using multivariate logistic regression, 13-HOTrE and 16(17)-EpDPE were the risk factors in the aortic patients group compared to healthy people (OR = 2.467, 95%CI:1.256–7.245, p = 0.035; OR = 0.015, 95%CI:0.0002–0.3240, p = 0.016, respectively). In KEGG enrichment of differential metabolites, the arachidonic acid metabolism pathway has the most metabolites involved. We established a diagnostic model in distinguishing between AD and healthy people. The AUC was 0.905. Oxylipins were significantly altered in AD patients, suggesting oxylipin profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.

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“…ATGL-deficient mice present severe micro- and macrovascular endothelial dysfunction [ 69 ], including impairment of vasodilatory, and reduction of eNOS/cGMP signaling. In human aortic endothelial cells (HAEC), silencing ATGL decreased the efficiency of stimulus-induced arachidonic acid (AA) release and prostacyclin secretion [ 70 ]. Adipose tissue microvascular endothelial cells (aMVECs) ATGL, but not HSL, plays an essential role in regulating adipose tissue lipid uptake through secreting PPARγ ligands [ 71 ].…”

Section: Endothelial Cell Metabolismmentioning

confidence: 99%

Fatty Acid Metabolism in Endothelial Cell

Liu

Dai

2022

Genes

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The endothelium is a monolayer of cells lining the inner blood vessels. Endothelial cells (ECs) play indispensable roles in angiogenesis, homeostasis, and immune response under normal physiological conditions, and their dysfunction is closely associated with pathologies such as cardiovascular diseases. Abnormal EC metabolism, especially dysfunctional fatty acid (FA) metabolism, contributes to the development of many diseases including pulmonary hypertension (PH). In this review, we focus on discussing the latest advances in FA metabolism in ECs under normal and pathological conditions with an emphasis on PH. We also highlight areas of research that warrant further investigation.

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Reduced expression of adipose triglyceride lipase decreases arachidonic acid release and prostacyclin secretion in human aortic endothelial cells

Cited by 21 publications

References 24 publications

Lipid droplets control mitogenic lipid mediator production in human cancer cells

Lipid droplets control mitogenic lipid mediator production in human cancer cells

Serum Oxylipin Profiles Identify Potential Biomarkers in Patients with Acute Aortic Dissection

Fatty Acid Metabolism in Endothelial Cell

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