3060-LB: A CAMKIIδ-EGR1 Proteostatic Checkpoint Enforces Inflammatory Resolution in Obesity

Introduction and Objective: Obesity-induced inflammation arises from failure to resolve transient immune responses, but the mechanism remain elusive. We studied whether CAMKIIδ enforces resolution by controlling adipose macrophages (ATMs). Methods: Macrophage Camk2d knockout (CKO) and WT mice were fed HFD. We assessed metabolic phenotypes and performed scRNA-seq, proteomics and kinase assays of ATMs. Results: Camk2d KO promotes obesity. scRNA-seq revealed expansion of pathogenic ATMs co-expressing lipid-handling and inflammatory programs. CAMKIIδ directly phosphorylated EGR1 at Ser378. In CKO mice, EGR1 stabilized, converting transient signaling into persistent inflammation. ATMs-specific Egr1 silencing reversed this disorder. Conclusion: CAMKIIδ-EGR1 axis acts as a post-translational timer enforcing inflammatory resolution, establishing a therapeutic target for obesity. Disclosure Y. Tu: None. C. Zheng: None.