Resistance training volume dictates distinct redox molecular signature in white adipose tissue: a high-sensitivity proteomics study.

Although white adipose tissue (WAT) serves as a dynamic storage organ that regulates overall metabolism, the molecular impacts of resistance training (RT) on WAT are still not fully understood. Considering that training variables influence RT outcomes, understanding the relationship between exercise volume and WAT remodeling is crucial for elucidating adaptive mechanisms. The hypothesis posits that a higher volume of RT, specifically 8 wk of climbing a vertical ladder for eight sets (RT-8), will lead to more significant positive adaptations in WAT remodeling than a lower volume of four sets (RT-4). The investigation combined histological, molecular (proteomic), and biochemical analyses (electron paramagnetic resonance, zymography, and enzyme-linked immunosorbent assay) with bioinformatics tools. By high-throughput mass spectrometry-based proteomics, we quantified 4,434 proteins in WAT of male rats and revealed that the RT-8 group displayed increased protein abundance associated with lipid transport, fatty acid unsaturation, and lipolysis compared with RT-4. In addition, compared with sedentary controls, RT-8 showed enhanced antioxidant capacity through phase II antioxidant enzymes (thioredoxins, peroxiredoxins, glutathione transferases, and ferritin). In contrast, the RT-4 group did not significantly alter the redox proteome, but selectively upregulated first-line antioxidant defense via the α-Klotho/superoxide dismutase/catalase axis. RT-4 was also associated with a reduction in reactive oxygen species production (superoxide ion and hydrogen peroxide), matrix metalloproteinase-2 activity, and adipocyte cross-sectional area to a similar extent as RT-8, without disrupting redox balance, ubiquitin ligase complex activity, or inflammatory pathways. Our findings contribute to the growing body of literature, suggesting that RT volume is a key determinant of the WAT proteomic signature, with training volume eliciting distinct molecular adaptations.NEW & NOTEWORTHY This study is the first to analyze how resistance training (RT) volume modulates white adipose tissue (WAT) remodeling. RT decreases adiposity index and adipocyte size regardless of exercise volume. Higher-volume RT shows greater abundance linked to phase II antioxidant enzymes and lipolysis pathways. However, inflammatory mediators and redox imbalance may be related to increased volume. Conversely, lower volume induces first-line antioxidant defense through α-Klotho upregulation, revealing that each volume dictates distinct regulatory mechanisms in WAT.