A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia | Zendy

Jeroen Baardman | Zendy; Sanne G. S. Verberk | Zendy; Koen H.M. Prange | Zendy; Michel van Weeghel | Zendy; Saskia van der Velden | Zendy; Dylan G. Ryan | Zendy; Rob C. I. Wüst | Zendy; Annette E. Neele | Zendy; Dave Speijer | Zendy; Simone Denis | Zendy; Maarten E. Witte | Zendy; Riekelt H. Houtkooper | Zendy; Luke O'neill | Zendy; Elena V. Knatko | Zendy; Albena T. DinkovaKostova | Zendy; Esther Lutgens | Zendy; Menno P.J. de Winther | Zendy; Jan Van den Bossche | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia

Author(s) -

Jeroen Baardman,

Sanne G. S. Verberk,

Koen H.M. Prange,

Michel van Weeghel,

Saskia van der Velden,

Dylan G. Ryan,

Rob C. I. Wüst,

Annette E. Neele,

Dave Speijer,

Simone Denis,

Maarten E. Witte,

Riekelt H. Houtkooper,

Luke O'neill,

Elena V. Knatko,

Albena T. DinkovaKostova,

Esther Lutgens,

Menno P.J. de Winther,

Jan Van den Bossche

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.10.092

Subject(s) - pentose phosphate pathway , macrophage , immune system , microbiology and biotechnology , inflammation , biology , macrophage polarization , metabolism , lipid metabolism , cytokine , chemistry , endocrinology , biochemistry , immunology , glycolysis , in vitro

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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research