哌啶酸
免疫系统
脂多糖
免疫
炎症
细胞因子
医学
败血症
免疫学
表观遗传学
内科学
内分泌学
生物
氨基酸
生物化学
基因
作者
Nini Zhang,Xinpei Wang,Mengya Feng,Min Li,Jing Wang,Hongyan Yang,Siyu He,Zhen‐hong Xia,Lei Shang,Xun Jiang,Sun Mao,Yuanming Wu,Chuan Ren,Xing Zhang,Jia Li,Feng Gao
标识
DOI:10.1038/s41467-024-47458-3
摘要
Abstract Exercise is usually regarded to have short-term beneficial effects on immune health. Here we show that early-life regular exercise exerts long-term beneficial effects on inflammatory immunity. Swimming training for 3 months in male mice starting from 1-month-old curbs cytokine response and mitigates sepsis when exposed to lipopolysaccharide challenge, even after an 11-month interval of detraining. Metabolomics analysis of serum and liver identifies pipecolic acid, a non-encoded amino acid, as a pivotal metabolite responding to early-life regular exercise. Importantly, pipecolic acid reduces inflammatory cytokines in bone marrow-derived macrophages and alleviates sepsis via inhibiting mTOR complex 1 signaling. Moreover, early-life exercise increases histone 3 lysine 4 trimethylation at the promoter of Crym in the liver, an enzyme responsible for catalyzing pipecolic acid production. Liver-specific knockdown of Crym in adult mice abolishes this early exercise-induced protective effects. Our findings demonstrate that early-life regular exercise enhances anti-inflammatory immunity during middle-aged phase in male mice via epigenetic immunometabolic modulation, in which hepatic pipecolic acid production has a pivotal function.
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