A microglial cell model for acyl-CoA oxidase 1 deficiency

Raas, Quentin; Saih, Fatima-Ezzahra; Gondcaille, Catherine; Trompier, Doriane; Hamon, Yannick; Leoni, Valerio; Caccia, Claudio; Nasser, Boubker; Jadot, Michel; Ménétrier, Franck; Lizard, Gérard; Cherkaoui‐Malki, Mustapha; Andreoletti, Pierre; Savary, Stéphane

doi:10.1016/j.bbalip.2018.10.005

Cited by 39 publications

(62 citation statements)

References 63 publications

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“…We could speculate that lipid metabolism, fatty acid synthesis and degradation in particular, might support a protective microglia phenotype, which could drive neuroprotection in neurodegenerative diseases. Furthermore, as we previously showed that peroxisomal FAO is a hallmark of M2 macrophages [73], and considering the novel roles of peroxisomes in immune cell functioning [74][75][76][77], it is of importance to also highlight this aspect of metabolism in microglia. In our study, we observed, in contrast to macrophages, no changes in peroxisomal FAO in polarized microglia.…”

Section: Discussionmentioning

confidence: 97%

Metabolic Reprogramming during Microglia Activation

et al. 2019

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Microglia, the specialized macrophages of the brain, can adopt different shapes and functions, some of which may be detrimental for nervous tissue. Similar to other immune cells, the metabolic program may determine the phenotypic features of microglia, and could constitute a therapeutic target in neurological diseases. Because the knowledge on microglial metabolism was sparse we here employed mouse primary microglia cells polarized into a pro- or anti-inflammatory state to define their metabolic features. After stimulation with either IL1β/IFNγ or IL4, the activity of glycolysis, glucose oxidation, glutamine oxidation, mitochondrial and peroxisomal fatty acid β-oxidation, and fatty acid synthesis, was assessed by using radiolabeled substrates. We complemented these data with transcriptome analysis of key enzymes orchestrating these metabolic pathways. Pro-inflammatory microglia exhibit increased glucose and glutamine metabolism and suppress both fatty acid oxidation and to a lesser extent fatty acid synthesis. On the other hand, anti-inflammatory microglia display changes only in fatty acid metabolism upregulating both fatty acid oxidation and fatty acid synthesis. Importantly, also human microglia-like cells differentiated from pluripotent stem cells upregulate glycolysis in pro-inflammatory conditions. Finally, we show that glycolytic enzymes are induced in a pro-inflammatory brain environment in vivo in mice. Taken together, the distinct metabolism in pro- and anti-inflammatory microglia can constitute a target to direct the microglial phenotype.

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Section: Discussionmentioning

confidence: 97%

Metabolic Reprogramming during Microglia Activation

et al. 2019

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“…It is well known that phagocytosis is affected by lipid membrane composition and is dependent on the extracellular and intracellular lipid environment. Peroxisome lipid metabolism has an extensive impact on lipid membrane composition, and peroxisome dysfunction leads to an unbalanced pool of cellular lipids necessary to support changes in immune cell membranes, which in turn affect the phagocytic capacity of a cell [10,[47][48][49]. Membrane properties are indeed modified by changes in their fatty acid and cholesterol content [50].…”

Section: Peroxisomes Turn On/off Pivotal Cellular Immune Signalingmentioning

confidence: 99%

Peroxisomes in host defense

Cara

2020

PLoS Pathog

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“…One of the hallmarks in these peroxisomal rare neurodegenerative diseases and in other common demyelinating disorders is the accompanying oxidative damage and neuroinflammation [3]. Compelling data indicates that oxidative stress can activate microglia leading to the overproduction of pro-inflammatory molecules [4,5]. Thus, targeting oxidative stress to limit neuroinflammation may open a new pharmacological therapy window for these still incurable devastating peroxisomal diseases.…”

mentioning

confidence: 99%