High-Intensity Interval Training and Monocyte Epigenetic Adaptation After Detraining

This randomized, work-matched training-detraining-rechallenge study evaluated whether repeated high-intensity interval training produces persistent functional and epigenetic adaptations in human monocytes. Eighty healthy physically inactive adults aged 18-30 years were randomly assigned in a 2:2:1 ratio to high-intensity interval training (HIIT), moderate-intensity continuous training (MCT), or a non-training control group. HIIT and MCT completed 6 weeks of supervised cycling training matched for external mechanical work, followed by 4 weeks without prescribed structured training. All groups subsequently completed a standardized 30-minute cycling rechallenge. The primary outcome was the between-group difference in change in ex-vivo LPS-stimulated TNF-alpha release from baseline to the post-detraining assessment. Secondary outcomes included IL-6 release, H3K18 lactylation, monocyte subset distribution, blood lactate exposure, chromatin accessibility, H3K18la CUT\&Tag occupancy, and RNA-seq transcriptional profiling.

Inclusion Men and women aged 18-30 years. Healthy adults. Physically inactive, defined as participating in less than 150 minutes per week of structured moderate-to-vigorous exercise during the preceding 6 months. Exclusion Criteria: * Major cardiovascular, metabolic, respiratory, renal, endocrine, inflammatory, autoimmune, or hematological disease. Current tobacco use. Current use of relevant immunomodulatory, anti-inflammatory, corticosteroid, or cardiovascular medications. Acute infection within 4 weeks before baseline assessment. Musculoskeletal contraindications to maximal cycling exercise. Pregnancy or lactation.