Highlights d LPS stimulates the PPP, SSP, and one-carbon metabolism d Glucose, serine, and methionine synergistically fuel SAM generation d Immunometabolite SAM promotes LPS-induced IL-1b production d SAM supports pro-inflammatory macrophages through H3K36me3
Graphical AbstractHighlights d NLRP3 inflammasome activation couples SREBP2 maturation d SCAP-SREBP2 translocation and S1P are required for optimal NLRP3 inflammasome activity d SCAP escorts both NLRP3 and SREBP2 by forming a ternary complex d SCAP-SREBP2 inhibition protects mice from systemic inflammation
Highlights d HDAC3 promotes IL-1b-dependent inflammation d HDAC3 restricts fatty acid oxidation for optimal NLRP3 inflammasome activation d HDAC3 translocates to mitochondria upon NLRP3 inflammasome activation d HDAC3 deacetylates HADHA at lysine 303 to restrain its enzyme activity
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