Impact of endothelial lipase on cellular lipid composition

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

doi:10.1016/j.bbalip.2012.03.006

Cited by 23 publications

(26 citation statements)

References 29 publications

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“…Previous work has shown that LIPG exerts phospholipase A1 activity towards high‐density lipoprotein (HDL)‐derived phosphatidylcholine (PC), releasing lipid products that become incorporated into intracellular PC and triacylglyceride (TAG) pools . Therefore, we investigated whether this also applies to breast cancer cells.…”

Section: Resultsmentioning

confidence: 96%

“…Previous work has shown that LIPG exerts phospholipase A1 activity towards high-density lipoprotein (HDL)-derived phosphatidylcholine (PC), 19 releasing lipid products that become incorporated into intracellular PC and triacylglyceride (TAG) pools. 7 Therefore, we investigated whether this also applies to breast cancer cells. First, endogenous expression of LIPG mRNA was measured in breast cancer cell lines of different subtypes: MCF-7 and T47D (ER+/HER2-), BT474 (ER +/HER2+), MDA-MB231 and MDA-MB-468 (ER-/HER2-) and SKBR3 and HCC1954 (ER-/HER2+).…”

Section: Lipg Enables Cancer Cells To Use Circulating Lipoproteins Asmentioning

confidence: 99%

“…LIPG was originally identified in endothelial cells as a further member of the triglyceride lipase family and is a cell surface‐associated lipase with predominantly phospholipase A1 activity. It cleaves phosphatidylcholine (PC) from high‐density lipoproteins (HDL), thereby releasing free fatty acids (FFAs) and lysophosphatidylcholine (LPC), which can be taken up by cells . Due to its impact on HDL metabolism, LIPG has over past decades been primarily studied in the context of cardiovascular disease.…”

Section: Introductionmentioning

confidence: 99%

“…It cleaves phosphatidylcholine (PC) from highdensity lipoproteins (HDL), thereby releasing free fatty acids (FFAs) and lysophosphatidylcholine (LPC), which can be taken up by cells. 7 Due to its impact on HDL metabolism, LIPG has over past decades been primarily studied in the context of cardiovascular disease. Studies on a role for LIPG in cancer are scarce.…”

Section: Introductionmentioning

confidence: 99%

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LIPG‐promoted lipid storage mediates adaptation to oxidative stress in breast cancer

Cadenas

Vosbeck

Edlund

et al. 2019

Intl Journal of Cancer

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Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high‐density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis‐free survival in node‐negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress‐induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression.

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Section: Resultsmentioning

confidence: 96%

Section: Lipg Enables Cancer Cells To Use Circulating Lipoproteins Asmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

LIPG‐promoted lipid storage mediates adaptation to oxidative stress in breast cancer

Cadenas

Vosbeck

Edlund

et al. 2019

Intl Journal of Cancer

Self Cite

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“…[31][32][33][34][35] In addition, the lipolytic products generated by EL in HDL were previously shown to exert both putatively pro-and antiatherogenic activities. [36][37][38][39] Indeed, Hara et al 37 reported that EL deletion resulted in increased HDL and anti-inflammatory function in the plasma compartment; Ahmed et al 39 showed that HDL lipolysis by EL mediates repression of vascular cell adhesion molecule 1 expression. In view of the many anti-inflammatory properties of HDL, 40 any increased transendothelial HDL transport and hence extravascular enrichment of HDL in inflammation may be a mechanism aimed at the resolution of tissue inflammation.…”

Section: Discussionmentioning

confidence: 99%

Interleukin 6 Stimulates Endothelial Binding and Transport of High-Density Lipoprotein Through Induction of Endothelial Lipase

Robert

Lehner

Frank

et al. 2013

ATVB

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Objective-In the reverse cholesterol transport pathway, high-density lipoprotein (HDL) passes the endothelial cell barrier by mechanisms involving the scavenger receptor class B type I and the ATP-binding cassette G1. However, little is known on how inflammation influences this transendothelial transport. Approach and Results-On stimulation with interleukin-6, cultivated primary endothelial cells showed increased binding and transport of 125 I-HDL without changing the expression of scavenger receptor class B type I and ATP-binding cassette G1. Therefore, we analyzed the involvement of endothelial lipase (EL), a known HDL-binding protein expressed by endothelial cells. Here, we show an increased EL expression after interleukin-6 stimulation. Moreover, using pharmacological inhibitors or RNA interference against EL, we demonstrated its participation in HDL binding and transport through the endothelium. Furthermore, adenovirus-mediated transfection of endothelial cells with either catalytically active or nonactive EL revealed that EL facilitates the endothelial binding and transport by both bridging and lipolysis of HDL. EL was also found responsible for the reduction of HDL particle size occurring during the specific transport through a monolayer of endothelial cells. Finally, pharmacological inhibition of EL reversed the inducing effect of interleukin-6 on HDL binding and transport.Conclusions-Interleukin-6 stimulates the translocation of HDL through the endothelium, the first step in reverse cholesterol transport pathway, by enhancing EL expression. In addition, we demonstrated the role of EL in the transendothelial transport of HDL. [13][14][15][16] Moreover, several groups demonstrated the upregulation of EL on inflammatory stimulation both in vitro and in vivo. [17][18][19][20] In this study, we provide evidence that EL participates in endothelial binding, cell association, and transport of HDL. Materials and MethodsMaterials and Methods are available in the online-only Supplement. Results IL-6 Induces HDL Binding, Cell Association, and TransportTo investigate whether the interaction of HDL with endothelial cells is changed by the inflammatory cytokine IL-6, we stimulated aortic endothelial cells with IL-6. The interaction of HDL with the endothelial cells was characterized as binding at 4°C, cell association and transport at 37°C. IL-6 induced HDL binding to endothelial cells in a dose-and timedependent manner ( Figure IA and IB in the online-only Data Supplement). HDL binding was significantly increased after incubation with 1-or 10-ng/mL IL-6. Because of the maximal effects seen, all subsequent experiments were performed on cells that were stimulated without 0-or 10-ng/mL IL-6 for 24 hours. After 24 hours of IL-6 stimulation, specific binding was induced by 200±67% compared with not stimulated cells (100±28%; Figure 1A). Conversely, the specific cellularassociated HDL and the transported HDL were also increased by 144±21% and 178±39%, respectively, compared with not stimulated cells (100±17%; Figure 1B a...

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LIPG is a novel prognostic biomarker and correlated with immune infiltrates in lung adenocarcinoma

Wang

Chen

et al. 2022

Clinical Laboratory Analysis

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Background Although many biomarkers for lung adenocarcinoma (LUAD) have been identified, their specificity and sensitivity remain unsatisfactory. Endothelial lipase gene (LIPG) plays an important role in a variety of cancers, but its role in lung adenocarcinoma remains unclear. Methods TCGA, GEO, K‐M plotter, CIBERSORT, GSEA, HPA, and GDSC were used to analyze LIPG in LUAD. Data analysis was mainly achieved by R 4.0.3. Results The expression of LIPG in LUAD tissues was higher than that in adjacent normal tissues, especially in women, patients aged >65 years, and those with lymph node metastasis. High expression predicted a poor prognosis. The results of enrichment analysis suggest that LIPG may exert profound effects on the development of LUAD through multiple stages of lipid metabolism and immune system regulation. In addition, LIPG expression was significantly correlated with the expression levels of multiple immune checkpoint genes and the abundance of multiple immune infiltrates, including the activated memory CD4 T cell, M1 macrophage, neutrophil, plasma cells, and T follicular helper (Tfh) cells in the LUAD microenvironment content. At the same time, patients with high LIPG expression respond well to a variety of antitumor drugs and have a low rate of drug resistance. Conclusions LIPG is a prognostic marker and is associated with lipid metabolism and immune infiltration in LUAD.

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Impact of endothelial lipase on cellular lipid composition

Cited by 23 publications

References 29 publications

LIPG‐promoted lipid storage mediates adaptation to oxidative stress in breast cancer

LIPG‐promoted lipid storage mediates adaptation to oxidative stress in breast cancer

Interleukin 6 Stimulates Endothelial Binding and Transport of High-Density Lipoprotein Through Induction of Endothelial Lipase

LIPG is a novel prognostic biomarker and correlated with immune infiltrates in lung adenocarcinoma

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