AUTHOR=Verberk Sanne G. S. , van der Zande Hendrik J. P. , Baardman Jeroen , de Goede Kyra E. , Harber Karl J. , Keuning Eelco D. , Lambooij Joost M. , Otto Frank , Zawistowska-Deniziak Anna , de Vries Helga E. , de Winther Menno P. J. , Guigas Bruno , Van den Bossche Jan TITLE=Myeloid ATP Citrate Lyase Regulates Macrophage Inflammatory Responses In Vitro Without Altering Inflammatory Disease Outcomes JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.669920 DOI=10.3389/fimmu.2021.669920 ISSN=1664-3224 ABSTRACT=
Macrophages are highly plastic, key regulators of inflammation. Deregulation of macrophage activation can lead to excessive inflammation as seen in inflammatory disorders like atherosclerosis, obesity, multiple sclerosis and sepsis. Targeting intracellular metabolism is considered as an approach to reshape deranged macrophage activation and to dampen the progression of inflammatory disorders. ATP citrate lyase (Acly) is a key metabolic enzyme and an important regulator of macrophage activation. Using a macrophage-specific Acly-deficient mouse model, we investigated the role of Acly in macrophages during acute and chronic inflammatory disorders. First, we performed RNA sequencing to demonstrate that Acly-deficient macrophages showed hyperinflammatory gene signatures in response to acute LPS stimulation