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Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice

ABSTRACT: Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice

PROVIDER: PRJNA1074089 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27887278_1.fastq.gz	Fastqsanger.gz
	SRR27887278_2.fastq.gz	Fastqsanger.gz
	SRR27887279_1.fastq.gz	Fastqsanger.gz
	SRR27887279_2.fastq.gz	Fastqsanger.gz
	SRR27887280_1.fastq.gz	Fastqsanger.gz

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Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice

Project description: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 curbed cytokine response and mitigated sepsis when exposed to lipopolysaccharide (LPS) challenge, even after 11-month interval of detraining. Metabolomics analysis of serum and liver identified pipecolic acid (a non-encoded amino acid) as a pivotal metabolite responding to early-life regular exercise. We then explored histone epigenetic modifications and observed a significant increase of H3K4me3 expression in the liver of 15-month-old mice exposed to early-life exercise. To further unravel the prolonged increased pipecplic acid production raised by early-life exercise, we conducted ChIP-seq analysis and found H3K4me3 occupancy at Crym (a key enzyme responsible for catalyzing pipecolic acid production) promoter has a significant increase in hepatocytes of early-life exercised mice. 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 plays a pivotal role.

2024-03-12 | GSE255161 | GEO

Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice.

Project description: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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Exercise training modifies the whole-blood methylation profile in middle-aged and older women

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