Please use this identifier to cite or link to this item: doi:10.22028/D291-38469
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Title: ACC1 (Acetyl Coenzyme A Carboxylase 1) Is a Potential Immune Modulatory Target of Cerebral Ischemic Stroke
Author(s): Wang, Xin
Zhou, Yuxi
Tang, Dan
Zhu, Ziyu
Li, Yan
Huang, Tingting
Müller, Rolf
Yu, Weifeng
Li, Peiying
Language: English
Title: Stroke
Volume: 50
Issue: 7
Pages: 1869-1878
Publisher/Platform: American Heart Association
Year of Publication: 2019
Free key words: brain
fatty acids
regulatory T cells
Th17 cells
DDC notations: 500 Science
Publikation type: Journal Article
Abstract: Background and Purpose—Cerebral ischemic stroke elicits profound responses of CD4+ T cells, which in turn significantly affect the ischemic brain injury. ACC1 (acetyl coenzyme A carboxylase 1) is a key enzyme that has been recently found to propagate CD4+ T cell–associated inflammation by mediating de novo fatty acid synthesis; however, its role in the context of ischemic stroke remains unknown. Methods—Focal cerebral ischemia was induced by transient middle cerebral artery occlusion for 60 minutes in mice. Seahorse XF glycolysis assay and targeted lipidomic profiling were used to detect metabolic changes in CD4+ T cell after stroke. CD4cre mice were crossed with ACC1fl/fl mice to generate the CD4+ T-cell–specific deletion of ACC1 (CD4creACC1fl/fl mice) mice. Pretreatment with calorie restriction (CR; with 30% reduction of food for 4 weeks before middle cerebral artery occlusion) or post-treatment with ACC1 inhibitor, soraphen A were both used to test the effect of ACC1 modulation on poststroke neuroinflammation. Results—Cerebral ischemic stroke increased glycolysis and fatty acid synthesis in peripheral CD4+ T cells, in which the expression of ACC1 was also upregulated. CR downregulated the expression of ACC1 in CD4+ T cells after stroke. Both CD4creACC1fl/fl mice and CR-pretreated mice exhibited significantly reduced ischemic brain injury and preserved the balance of peripheral regulatory T cells/T helper 17 (Th17) cells. Furthermore, conditional knockout of ACC1 in CD4+ T cells attenuated the protection exerted by CR both on ischemic brain injury and peripheral balance of regulatory T cells/ Th17 cells. Pharmacological inhibition of ACC1 after middle cerebral artery occlusion attenuates neuroinflammation, preserves regulatory T cells/Th17 balance, and improves neurological outcomes after ischemic stroke. Conclusions—ACC1 is a novel immune metabolic modulation target to balance the regulatory T cells and Th17 cells and blunt neuroinflammation after stroke. Inhibition of ACC1 can be a previously unrecognized mechanism that underlies CR-afforded neuroprotection against cerebral ischemic stroke.
DOI of the first publication: 10.1161/STROKEAHA.119.024564
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-384697
ISSN: 1524-4628
Date of registration: 8-Dec-2022
Description of the related object: Supplemental Material
Related object:
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Pharmazie
Professorship: NT - Prof. Dr. Rolf Müller
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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