| Literature DB >> 30463003 |
Jeroen Baardman1, Sanne G S Verberk2, Koen H M Prange1, Michel van Weeghel3, Saskia van der Velden1, Dylan G Ryan4, Rob C I Wüst5, Annette E Neele1, Dave Speijer1, Simone W Denis3, Maarten E Witte2, Riekelt H Houtkooper3, Luke A O'neill4, Elena V Knatko6, Albena T Dinkova-Kostova7, Esther Lutgens8, Menno P J de Winther8, Jan Van den Bossche9.
Abstract
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.Entities:
Keywords: Nrf2; atherosclerosis; cardiovascular disease; foam cells; hypercholesterolemia; immunometabolism; inflammation; macrophages; meta-inflammation; metabolic disease; pentose phosphate pathway
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Year: 2018 PMID： 30463003 DOI： 10.1016/j.celrep.2018.10.092
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423