Transcriptomic Profiling of scWAT Reveals Reduced Lipid-Associated Macrophage Signatures in Long-Term Endurance- and Resistance-Trained Athletes

Abstract

Regular exercise training is associated with systemic and tissue-specific performance and health benefits, yet long-term molecular adaptations in subcutaneous abdominal white adipose tissue (scWAT) remain unclear. We analyzed the resting scWAT transcriptome of 89 adults (35-50 years) who were long-term (>15 years) endurance- or strength-trained, or untrained. Long-term training was linked to enrichment of ribosomal, mitochondrial, and aerobic metabolism-related pathways, while immune-related pathways were enriched in untrained individuals. A distinct sex dimorphic scWAT was identified: untrained females exhibited a more metabolically favorable, trained-like transcriptomic profile, and untrained males an untrained-like profile. In trained males, the inflammatory gene signature was lower than in untrained males. We also identified 11 genes specific to lipid-associated macrophages with lower expression in trained individuals, particularly in all endurance-trained individuals and strength-trained females. These findings highlight sex-specific, exercise-induced adaptations in scWAT relevant to metabolic health, and underscore the importance of including both sexes in scWAT research.