A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia
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 transcripti...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718316966 |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 W. Denis Maarten E. Witte Riekelt H. Houtkooper Luke A. O’neill Elena V. Knatko Albena T. Dinkova-Kostova Esther Lutgens Menno P.J. de Winther Jan Van den Bossche |
| spellingShingle |
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 W. Denis Maarten E. Witte Riekelt H. Houtkooper Luke A. O’neill Elena V. Knatko Albena T. Dinkova-Kostova Esther Lutgens Menno P.J. de Winther Jan Van den Bossche A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia Cell Reports |
| author_facet |
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 W. Denis Maarten E. Witte Riekelt H. Houtkooper Luke A. O’neill Elena V. Knatko Albena T. Dinkova-Kostova Esther Lutgens Menno P.J. de Winther Jan Van den Bossche |
| author_sort |
Jeroen Baardman |
| title |
A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia |
| title_short |
A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia |
| title_full |
A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia |
| title_fullStr |
A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia |
| title_full_unstemmed |
A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia |
| title_sort |
defective pentose phosphate pathway reduces inflammatory macrophage responses during hypercholesterolemia |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2018-11-01 |
| description |
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. : The link between systemic and cellular metabolism is a neglected aspect in immunometabolism. Baardman et al. show that hypercholesterolemia alters macrophage metabolism and phenotype. The suppressed pentose phosphate pathway (PPP) in those “foam cell” macrophages attenuates inflammatory responses, signifying that systemic and cellular metabolism together regulate macrophage function. Keywords: immunometabolism, inflammation, macrophages, hypercholesterolemia, pentose phosphate pathway, Nrf2, meta-inflammation, foam cells, atherosclerosis, cardiovascular disease, metabolic disease |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124718316966 |
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doaj-d4969ea3a1584cdbbc7e5b1d85f556122020-11-25T00:27:23ZengElsevierCell Reports2211-12472018-11-0125820442052.e5A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during HypercholesterolemiaJeroen Baardman0Sanne G.S. Verberk1Koen H.M. Prange2Michel van Weeghel3Saskia van der Velden4Dylan G. Ryan5Rob C.I. Wüst6Annette E. Neele7Dave Speijer8Simone W. Denis9Maarten E. Witte10Riekelt H. Houtkooper11Luke A. O’neill12Elena V. Knatko13Albena T. Dinkova-Kostova14Esther Lutgens15Menno P.J. de Winther16Jan Van den Bossche17Amsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsAmsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HZ Amsterdam, the NetherlandsAmsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsAmsterdam UMC, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsAmsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, IrelandAmsterdam UMC, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of Biomedical Engineering and Physics, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsAmsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsAmsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsAmsterdam UMC, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsAmsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HZ Amsterdam, the NetherlandsAmsterdam UMC, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the NetherlandsSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, IrelandJacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee DD1 9SY, UKJacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee DD1 9SY, UK; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USAAmsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilians University, Pettenkoferstrasse 9, 80336 Munich, GermanyAmsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Institute for Cardiovascular Prevention (IPEK), Ludwig Maximilians University, Pettenkoferstrasse 9, 80336 Munich, GermanyAmsterdam UMC, University of Amsterdam, Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Cardiovascular Sciences, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HZ Amsterdam, the Netherlands; Corresponding authorSummary: 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 link between systemic and cellular metabolism is a neglected aspect in immunometabolism. Baardman et al. show that hypercholesterolemia alters macrophage metabolism and phenotype. The suppressed pentose phosphate pathway (PPP) in those “foam cell” macrophages attenuates inflammatory responses, signifying that systemic and cellular metabolism together regulate macrophage function. Keywords: immunometabolism, inflammation, macrophages, hypercholesterolemia, pentose phosphate pathway, Nrf2, meta-inflammation, foam cells, atherosclerosis, cardiovascular disease, metabolic diseasehttp://www.sciencedirect.com/science/article/pii/S2211124718316966 |