Regular exercisers show distinct metabolic and immune signatures in blood

by · News-Medical

A detailed analysis of blood samples from 86 adults examines how exercise habits relate to energy metabolism and immune cell behavior.

Study: Multiomics profiling identifies molecular and cellular signatures of regular exercise in human peripheral blood. Image Credit: muse studio / Shutterstock

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A recent study published in the journal Science Advances found differences in blood metabolites and immune cell profiles between adults who exercised regularly and those who were sedentary. These differences involved glucose and lipid metabolism, metabolites consistent with fatty acid oxidation (FAO), antioxidant-related metabolites, and immune signaling.

Some immune cell analyses suggested weaker inflammatory signaling among exercisers, but the study did not establish a reduction in systemic inflammation. The findings identify candidate biomarkers and regulatory pathways for future investigation.

The health benefits of regular physical activity for immune function and disease prevention are well established. Yet the biological mechanisms underlying these protective effects are unclear. Much of the previous mechanistic research involved short-term studies conducted in controlled settings or among selected populations, highlighting the need for further research in real-world contexts.

About the study

In the present study, researchers compared molecular signatures among regularly exercising (EX, n=40) and sedentary (SED, n=46) individuals. To do so, they collected information and blood samples from participants of the Chinese Immune Multi-omics Atlas (CIMA) study. They then performed a comprehensive set of evaluations, ranging from plasma lipidomics and metabolomics to single-cell transcriptomics and epigenomic assessments.

In addition to single-cell ribonucleic acid sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), intercellular communication analysis was also performed to infer signaling between immune cells. Differentially expressed gene and gene ontology analyses helped the team dissect exercise-related alterations in myeloid cell populations.

Non-obese individuals (body mass index [BMI] <30 kg/m²) aged 20 to 40 years who self-reported being disease-free and non-pregnant were recruited for the study between November 2021 and the same period in the following year. Smokers and people with a history of cancer or chronic infectious disease were excluded. Based on participants' self-reported exercise, the team classified them into two groups using criteria informed by the World Health Organization (WHO) guidelines.

The EX group comprised 40 individuals who engaged in planned exercise at least 3 times per week, accumulating ≥75 min of vigorous-intensity or ≥150 min of moderate-intensity activity each week. The SED group included 46 individuals who reported no purposeful exercise and predominantly sat during the day. Using statistical models adjusted for sex and BMI, with age included in some analyses, the researchers evaluated molecular differences between the EX and SED groups.

Results

The participants were young (mean age, 28 years) with a healthy weight (mean BMI, 21.3 kg/m²). Among them, regular physical exercise was associated with blood metabolite patterns consistent with greater fatty acid utilization, mitochondrial fatty acid transport, and ketone production, as well as higher concentrations of certain antioxidant-related metabolites. The groups also differed in immune cell gene expression and chromatin accessibility.

Compared with the SED group, regularly exercising individuals had significantly lower triglyceride (TG) and fasting blood glucose (GLU) levels, and significantly higher concentrations of high-density lipoprotein (HDL) cholesterol. The levels of bilirubin, uric acid, and creatinine were also significantly higher in the EX group. The higher bilirubin and uric acid concentrations may reflect stronger antioxidant defenses, whereas creatinine could reflect differences in muscle metabolism; muscle mass was not measured.

Several metabolites related to energy metabolism, amino acid turnover, and fatty acid use, including p-hydroxymandelic acid and O-adipoylcarnitine, were more abundant in the EX group. Many triacylglycerols (TAG) and several complex phospholipids, such as phosphatidylcholine, phosphatidylglycerol, lysophosphatidylethanolamine, and phosphatidylinositol, were lower among regularly exercising individuals.

Plasma concentrations of betaine (a metabolite with reported anti-inflammatory properties) and 3-hydroxyanthranilic acid (which has antioxidant activity) were significantly greater in exercising participants. In the EX group, the team also observed an increase in xanthurenic acid and γ-aminobutyric acid (GABA), both of which have been implicated in regulating immune cell function. Among physically active individuals, the microbially derived compounds indoleacrylic acid and phenyllactic acid were also more abundant.

Earlier research has linked indoleacrylic acid to gut barrier function and immune regulation, but this study did not measure gut barrier function or establish that these metabolites reduced systemic inflammation.

The antigen-presenting cells (APCs) of physically active individuals, particularly B cells and classical monocytes, showed simultaneous increases in chromatin accessibility and antigen presentation gene transcription. In myeloid cells, the researchers also found increased expression of genes associated with leukocyte chemotaxis.

In addition, natural killer (NK) and cytotoxic T cells exhibited epigenetic changes consistent with greater potential for immune activation. Cell-communication models predicted stronger major histocompatibility complex I/II (MHC-I/II)-mediated interactions between T cells and APCs, and weaker inflammatory signaling.

Among participants who exercised regularly, lower promoter accessibility of C-X-C motif chemokine ligand 8 (CXCL8) was associated with lower CXCL8 messenger RNA (mRNA) expression, while models suggested weaker proinflammatory interleukin-6 (IL-6) signaling.

Analyses also indicated stronger interferon signaling and greater inferred regulatory activity of transcription factors such as signal transducer and activator of transcription 1 (STAT1).

Conclusion

The findings suggest that regular exercise is associated with changes in metabolic and immune networks that may contribute to cardiometabolic health, but future studies are required to assess causality. These findings could guide further research on potential biomarkers and the mechanisms behind exercise-related health benefits.

The study also relied on a small, largely young and healthy sample, lacked long-term exercise histories, and did not have every type of molecular data for every participant. The groups differed in sex composition; an analysis restricted to women revealed broadly consistent trends in gene expression and chromatin accessibility. Individual metabolite and pathway results were exploratory.

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