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| Status |
Public on Oct 31, 2018 |
| Title |
A defective pentose phosphate pathway reduces inflammatory macrophage responses during hypercholesterolemia |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Metabolic reprogramming has emerged as a crucial regulator of immune cell activation but how systemic metabolism influences immune cell metabolism and function remains to be investigated. To investigate the effect of dyslipidemia on immune cell metabolism, we performed in-depth transcriptional, metabolic and functional characterization of macrophages isolated from hypercholesterolemic mice. Systemic metabolic changes in such mice alter cellular macrophage metabolism and attenuate inflammatory macrophage responses. In addition to diminished maximal mitochondrial respiration, hypercholesterolemia reduces the LPS-mediated induction of the pentose phosphate pathway (PPP) and the Nrf2-mediated oxidative stress response. Our observation that suppression of the PPP diminishes LPS-induced cytokine secretion supports the notion that this pathway contributes to inflammatory macrophage responses. Overall, this study reveals that systemic and cellular metabolism are strongly interconnected, together dictating macrophage phenotype and function.
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| Overall design |
RNA-seq of peritoneal macrophages from female mice placed on a control or high fat diet, stimulated with LPS for 0 or 24 hours.
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| Contributor(s) |
Baardman J, Verberk SG, Prange KH, Weeghel M, van der Velden S, Ryan DG, Wüst RC, Neele AE, Speijer D, Denis SW, Witte ME, Houtkooper RH, O'Neill LA, Knatko EV, Dinkova-Kostova AT, Lutgens E, de Winther MP, van den Bossche J |
| Citation(s) |
30463003 |
| Submission date |
Nov 28, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Menno de Winther |
| E-mail(s) |
m.dewinther@amc.uva.nl
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| Phone |
+31205666762
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| Organization name |
Academic Medical Center University of Amsterdam
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| Department |
Medical Biochemistry
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| Lab |
Experimental Vascular Biology
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| Street address |
Meibergdreef 9
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| City |
Amsterdam |
| ZIP/Postal code |
1105AZ |
| Country |
Netherlands |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA420032 |
| SRA |
SRP125735 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE107412_readcounts.txt.gz |
651.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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