Lipid droplets in activated mast cells – a significant source of triglyceride-derived arachidonic acid for eicosanoid production

Dichlberger, Andrea; Schlager, Stefanie; Kovanen, Petri T.; Schneider, Wolfgang J.

doi:10.1016/j.ejphar.2015.07.020

Cited by 32 publications

(26 citation statements)

References 145 publications

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“…Similarly, adipose tissue as a whole, and the macrophages isolated from it show increased PUFA levels in the obese setting and elevated TAG [50]. TAG are stored in mast cell LB [11]. Our analysis suggests that under the hyperinsulinaemic conditions modelled in our experiments, mast cells show increases in PUFA but marginal increases overall in TAG.…”

Section: Discussionsupporting

confidence: 51%

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Insulin-induced lipid body accumulation is accompanied by lipid remodelling in model mast cells

et al. 2019

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Mast cell lipid bodies are key to initiation, maintenance and resolution of inflammatory responses in tissue. Mast cell lines, primary bone marrow-derived mast cells and peripheral blood basophils present a 'steatotic' phenotype in response to chronic insulin exposure, where cells become loaded with lipid bodies. Here we show this state is associated with reduced histamine release, but increased capacity to release bioactive lipids. We describe the overall lipid phenotype of mast cells in this insulin-induced steatotic state and the consequences for critical cellular lipid classes involved in stages of inflammation. We show significant insulin-induced shifts in specific lipid classes, especially arachidonic acid derivatives, MUFA and PUFA, the EPA/DHA ratio, and in cardiolipins, especially those conjugated to certain DHA and EPAs. Functionally, insulin exposure markedly alters the FcεRI-induced release of Series 4 leukotriene LTC4, Series 2 prostaglandin PGD2, Resolvin-D1, Resolvin-D2 and Resolvin-1, reflecting the expanded precursor pools and impact on both the pro-inflammation and pro-resolution bioactive lipids that are released during mast cell activation. Chronic hyperinsulinemia is a feature of obesity and progression to Type 2 Diabetes, these data suggest that mast cell release of key lipid mediators is altered in patients with metabolic syndrome.

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Section: Discussionsupporting

confidence: 51%

“…However, qualitative changes in the cellular profiles of bioactive lipids and their precursors have not been extensively explored. This is an important question arising from the marked effects that lipid remodelling has upon the net pro-and anti-inflammatory capacity of cells such as mast cells [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Insulin-induced lipid body accumulation is accompanied by lipid remodelling in model mast cells

et al. 2019

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“…Lipid droplets may have multiple functional roles. They serve as an energy store (Kimmel & Sztalryd, ), buffer against fatty acid peroxidation (Bailey et al., ), and as a site for eicosanoid synthesis from fatty acids may contribute to inflammation and degeneration (Dichlberger, Schlager, Kovanen, & Schneider, ). Lipid droplets are suggested to represent an early marker for apoptosis (Boren & Brindle, ) and neurodegeneration (Liu et al., ).…”

Section: Discussionmentioning

confidence: 99%

Lipid markers and related transcripts during excitotoxic neurodegeneration in kainate‐treated mice

Chali

Milior

Marty

et al. 2019

Eur J of Neuroscience

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Lipid homeostasis is dysregulated in some neurodegenerative diseases and after brain injuries due to excess glutamate or lack of oxygen. However the kinetics and cell specificity of dysregulation in different groups of lipids during excitotoxic neuronal death are not clear. Here we examined the changes during excitotoxic neuronal death induced by injecting kainic acid (KA) into the CA1 region of mouse hippocampus. We compared neuronal loss and glial cell proliferation with changes in lipid‐related transcripts and markers for different lipid groups, over 12 days after KA‐treatment. As neurons showed initial signs of damage, transcripts and proteins linked to fatty acid oxidation were up‐regulated. Cholesterol biosynthesis induced by transcripts controlled by the transcription factor Srebp2 seems to be responsible for a transient increase in neuronal free cholesterol at 1 to 2 days. In microglia, but not in neurons, Perilipin‐2 associated lipid droplets were induced and properties of Nile red emissions suggest lipid contents change over time. After microglial expression of phagocytotic markers at 2 days, some neutral lipid deposits co‐localized with lysosome markers of microglia and were detected within putative phagocytotic cups. These data delineate distinct lipid signals in neurons and glial cells during excitotoxic processes from initial neuronal damage to engagement of the lysosome–phagosome system.

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“…Finally, the breakdown of lipid droplets provides FAs and other lipids that act as signalling molecules by themselves—e.g., by interacting with transcription factors such as peroxisome proliferator-activated receptors (PPARs) and sterol-regulatory element binding proteins (SREBPs)—or they are converted into bioactive lipid mediators, such as eicosanoids, that act as paracrine and autocrine messengers affecting inflammatory signalling, metabolism, proliferation, migration, and metastasis [ 14 , 63 , 64 , 65 , 66 ]. This emerging aspect of lipid droplet biology will not be covered in this review, but we would like to refer the reader to several excellent recent reviews [ 13 , 18 , 67 , 68 , 69 ].…”

Section: Introductionmentioning

confidence: 99%

Lipid Droplets in Cancer: Guardians of Fat in a Stressful World

2018

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Cancer cells possess remarkable abilities to adapt to adverse environmental conditions. Their survival during severe nutrient and oxidative stress depends on their capacity to acquire extracellular lipids and the plasticity of their mechanisms for intracellular lipid synthesis, mobilisation, and recycling. Lipid droplets, cytosolic fat storage organelles present in most cells from yeast to men, are emerging as major regulators of lipid metabolism, trafficking, and signalling in various cells and tissues exposed to stress. Their biogenesis is induced by nutrient and oxidative stress and they accumulate in various cancers. Lipid droplets act as switches that coordinate lipid trafficking and consumption for different purposes in the cell, such as energy production, protection against oxidative stress or membrane biogenesis during rapid cell growth. They sequester toxic lipids, such as fatty acids, cholesterol and ceramides, thereby preventing lipotoxic cell damage and engage in a complex relationship with autophagy. Here, we focus on the emerging mechanisms of stress-induced lipid droplet biogenesis; their roles during nutrient, lipotoxic, and oxidative stress; and the relationship between lipid droplets and autophagy. The recently discovered principles of lipid droplet biology can improve our understanding of the mechanisms that govern cancer cell adaptability and resilience to stress.

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Lipid droplets in activated mast cells – a significant source of triglyceride-derived arachidonic acid for eicosanoid production

Cited by 32 publications

References 145 publications

Insulin-induced lipid body accumulation is accompanied by lipid remodelling in model mast cells

Insulin-induced lipid body accumulation is accompanied by lipid remodelling in model mast cells

Lipid markers and related transcripts during excitotoxic neurodegeneration in kainate‐treated mice

Lipid Droplets in Cancer: Guardians of Fat in a Stressful World

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