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Large-scale multi-species survey of metabolome and lipidome

ABSTRACT: Large-scale multi-species survey of metabolome and lipidome

PROVIDER: PRJNA213747 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR945190.fastq.gz	Fastqsanger.gz
	SRR945191.fastq.gz	Fastqsanger.gz
	SRR945192.fastq.gz	Fastqsanger.gz
	SRR945193.fastq.gz	Fastqsanger.gz
	SRR945194.fastq.gz	Fastqsanger.gz

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Project description:Microglia are specialized immune cells in the brain that eliminate misfolded protein deposits and cellular debris by phagocytosis. In Alzheimers disease, microglia clear the amyloid beta aggregates during disease onset but are unable to phagocytose them from the tissue environment during the late stages of the disease contributing to chronic inflammation. Lipids and metabolites orchestrate critical regulation events within the cell or by their secretion into the cellular microenvironment, yet, the effect of abeta on microglial lipidome and metabolome has not been well characterized till date. In this study, we used Multiple-Reaction Monitoring (MRM)-profiling to evaluate, for the first time, the lipid and metabolite changes in abeta-activated microglia that were isolated from mouse brains over 24 hours. We also developed a new bioinformatics pipeline to identify the statistically significant lipids and metabolites in abeta-treated microglial cells and condition medium that were differentially regulated compared to the vehicle controls. Triacylglycerides and phosphatidylglycerols were the most abundant lipid classes, whereas long-chain free fatty acids with 26 to 30 acyl chain carbon atoms were consistently decreased with abeta-treatment over time. Further, 42 significant metabolites were identified in cells. L-2-aminobutyric acid, hydroxybutyric acid, inosine, alanine, etc. were differentially regulated with abeta treatment suggesting changes in alanine, aspartate and glutamate metabolism, and arginine biosynthesis pathways. Selected metabolites were identified in the microglial conditioned medium, including stearic acid, tryptophan, palmitic acid, etc. that have been shown to affect the phagocytic properties of peripheral macrophages and may also play a role in the microglial phagocytic response. Thus, characterizing the lipidome and metabolome of microglia due to abeta identifies critical molecules involved in their immune response and highlight the molecular mechanisms of phagocytic function as well as dysfunction associated with AD.

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Large-scale multi-species survey of metabolome and lipidome

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