The metabolic inflammation (meta-inflammation) of obesity is characterized by proinflammatory macrophage infiltration into adipose tissue. Catalysis by deoxyhypusine synthase (DHPS) modifies the translation factor eIF5A to generate a hypusine (Hyp) residue. Hypusinated eIF5A (eIF5A^Hyp) controls the translation of mRNAs involved in inflammation, but its role in meta-inflammation has not been elucidated. Levels of eIF5A^Hyp were found to be increased in adipose tissue macrophages from obese mice and in murine macrophages activated to a proinflammatory M1-like state. Global proteomics and transcriptomics revealed that DHPS deficiency in macrophages altered the abundance of proteins involved in NF-κB signaling, likely through translational control of their respective mRNAs. DHPS deficiency in myeloid cells of obese mice suppressed M1 macrophage accumulation in adipose tissue and improved glucose tolerance. These findings indicate that DHPS promotes the post-transcriptional regulation of a subset of mRNAs governing inflammation and chemotaxis in macrophages and contributes to a proinflammatory M1-like phenotype.

肥胖的代谢性炎症（meta-inflammation）的特征是促炎性巨噬细胞浸润到脂肪组织中。脱氧海普辛合成酶 (DHPS) 的催化修饰翻译因子 eIF5A 以产生海普辛 (Hyp) 残基。Hypusinated eIF5A (eIF5A ^Hyp ) 控制与炎症相关的 mRNA 的翻译，但其在元炎症中的作用尚未阐明。eIF5A ^Hyp水平发现在来自肥胖小鼠的脂肪组织巨噬细胞和激活至促炎 M1 样状态的小鼠巨噬细胞中增加。全球蛋白质组学和转录组学表明，巨噬细胞中的 DHPS 缺乏改变了参与 NF-κB 信号传导的蛋白质的丰度，可能是通过对其各自 mRNA 的翻译控制。肥胖小鼠骨髓细胞中的 DHPS 缺乏抑制了 M1 巨噬细胞在脂肪组织中的积累并改善了葡萄糖耐量。这些发现表明，DHPS 促进了控制巨噬细胞炎症和趋化性的 mRNA 子集的转录后调节，并有助于促炎 M1 样表型。