Monocyte Genomic Response To Exercise: Implications For Inflammatory Pathways And Cardiovascular Disease Risk In Youth

Monocytes, an innate immune cell subtype, influence inflammation and vascular health. Biological sex impacts exercise gene expression in leukocytes collectively, but little is known about specific responses of monocytes in adolescents. We hypothesized, that genomic monocyte responses to exercise would be: 1) related to inflammation and cardiovascular health; and 2) influenced by sex. PURPOSE: To identify monocyte gene expression in response to acute exercise in adolescents. METHODS: 9 females and 12 males (14-17 y/o) performed ten 2-min exercise bouts at constant work of 71% (females) and 72% (males) of maximum work rate, interspersed with 1-min rest. Blood was obtained before and immediately after exercise. Monocytes were isolated (Miltenyi Biotec), and RNA-seq was performed. R package limma (v3.50.3) was used to perform differential gene expression analysis (FDR < 0.1) and DAVID Bioinformatics tool to identify significantly enriched KEGG Pathways (EASE score < 0.05). RESULTS: Exercise altered a greater number of genes in females (5137) compared to males (568). Genes were enriched in COVID-19 gene pathway in both sexes. In the males only: gene pathways were identified in TNF Signaling, Fluid Shear Stress, and Atherosclerosis; in the females: Adipocytokine Signaling, ErbB Signaling, EGFR Tyrosine Kinase Inhibitor Resistance. CONCLUSION: Exercise gene expression in males was 11% of female expression. The COVID-19 pathway was affected in both sexes, as were genes involved in immune regulation, suggesting that exercise modulates inflammation in all adolescents. Pathways linked to vascular health predominated in males, while pathways responsible for adipose cell crosstalk were found in females. Mechanisms responsible for the large sexual dimorphism in gene expression remains unknown. Monocyte gene expression in response to brief exercise may help provide insight and prevention strategies for pediatric origins of adult diseases and lead to sex-specific precision of the exercise prescription in adolescents. NIH Grant No.: U01 TR002004 (REACH project)