scholarly journals Lipid droplets are required for lipid mediator production and cancer cell proliferation

2021 ◽  
Author(s):  
Toni Petan ◽  
Thomas O. Eichmann ◽  
Robert Zimmermann ◽  
Anja Pucer Janež ◽  
Jana Gerstmeier ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Proliferation ◽  
Fatty Acid ◽  
Cancer Cell ◽  
Lipid Droplet ◽  
Lipid Droplets ◽  
Lipid Mediators ◽  
Lipid Mediator ◽  
Cancer Cell Proliferation ◽  
Membrane Phospholipids

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.

Effect on cancer cell proliferation of palmitoylethanolamide, a fatty acid amide interacting with both the cannabinoid and vanilloid signalling systems

2002 ◽  
Vol 16 (4) ◽  
pp. 297-302 ◽  
Author(s):  
Luciano De Petrocellis ◽  
Tiziana Bisogno ◽  
Alessia Ligresti ◽  
Maurizio Bifulco ◽  
Dominique Melck ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Fatty Acid ◽  
Cancer Cell ◽  
Acid Amide ◽  
Cancer Cell Proliferation ◽  
Signalling Systems ◽  
Fatty Acid Amide

Abstract 702: Walnut Treatment Reduces Specific Pro-inflammatory Lipid Mediators While Increasing Anti-inflammatory Ones: An RCT subanalysis

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Gregory C Shearer ◽  
John W Newman ◽  
Roberta R Holt ◽  
Carl L Keen ◽  
Robert M Hackman
Keyword(s):  
Fatty Acids ◽  
Heart Disease ◽  
Fatty Acid ◽  
Inflammatory Responses ◽  
Plasma Lipid ◽  
Lipid Mediators ◽  
Lipid Mediator ◽  
Plasma Fatty Acid ◽  
Anti Inflammatory ◽  
Active Dose

Background: Lipid mediators are transported in plasma, inducing pro- or anti-inflammatory responses in target tissues. Each daily nut serving is associated with 30% reduction in risk for cardiovascular or ischemic heart disease. Walnuts are an abundant source of bioactives and of precursors to lipid mediator synthesis: linoleic (LA) and alpha-linolenic (aLA) acids. How walnuts impact plasma lipid mediators either by providing more substrate or more specifically via other bioactives is unknown. Objective: Measure lipid mediators from the cyclooxygenase (COX), lipoxygenase (LOX), cytochrome p450 (CYP), and auto-oxidative pathways in plasma from subjects consuming large and small amounts of walnuts. Design: 40 hypercholesterolemic, postmenopausal females were randomly assigned to a null dose (5g/d) or an active dose (40 g/d) of walnuts for 4 weeks. In a subset of 20 subjects, plasma lipid mediators synthesized from LA, aLA and other polyunsaturated fatty acids were measured by LC/MS/MS at baseline and final visits. Differences are reported as mean, 95% CIs. Results: Walnuts did not alter the compositional abundance of any plasma fatty acid except aLA, which was increased 1.46 fold [1.83, 1.16], p=0.003. Walnuts did modify plasma lipid mediator composition: specific pro-inflammatory COX metabolites, PGD2 and PGJ2/delta-12-PGJ2 were reduced by -72% [-43, -86] and -55% [-9, -77] respectively. LOX metabolites were almost uniformly depressed: the immediate mid-chain alcohols of LA (HODEs), dgLA (HETrEs), AA (HETEs), EPA (HEPEs) and DHA (HDoHEs) were reduced by 50-75% (p≤0.007), but aLA (HOTEs) were not. Metabolites of 5-LOX further downstream were also reduced: 5-KETE by 79% [-91, -50], and 6-trans-LTB4 by -89% [-76, -95]. Conversely, anti-inflammatory CYP-epoxides of LA (EpOME) and aLA (EpODE) were increased 82% [3, 223] and 143% [37, 331]. Epoxides of eicosanoids and docosanoids were unchanged (AA EpETrEs or EETs; EPA EpETEs; DHA EpDPEs). Conclusion: Walnut feeding reduces plasma pro-inflammatory COX and LOX metabolites while increasing some anti-inflammatory CYP metabolites. The effect occurs largely without changes in fatty acids, suggesting a molecular mechanism independent of simple changes in precursor abundance.

scholarly journals Marine- and plant-derived ω-3 fatty acids differentially regulate prostate cancer cell proliferation

2013 ◽  
Vol 1 (3) ◽  
pp. 444-452 ◽  
Author(s):  
PINAR O. ESER ◽  
JOHN P. VANDEN HEUVEL ◽  
JOHN ARAUJO ◽  
JERRY T. THOMPSON
Keyword(s):  
Prostate Cancer ◽  
Fatty Acids ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Proliferation
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