High-Intensity Interval Exercise Drives Vitamin D Receptor Expression in Skeletal Muscle via Recruitment of Non-Parenchymal Cells, Not Upregulation in Muscle Fibers

<b>Background:</b> High-intensity interval exercise (HIIE) is gaining interest as an alternative to traditional moderate-intensity exercise due to its shorter exercise regimens. Yet, it still induces significant muscular adaptations, including metabolic remodeling, enhanced mitochondrial biogenesis, and improved endurance capacity. Exercise has been shown to increase vitamin D receptor (VDR) expression acutely; however, the role of this effect and whether it occurs during HIIE remain to be elucidated. <b>Objectives/Methods</b>: Here, we investigated the time-dependent effects of a single bout of high-intensity interval exercise (HIIE) on systemic inflammatory cytokine profiles and gene expression, including VDR, in aged skeletal muscle. Sedentary aged mice (male C57Bl/6J at 24 months of age) were provided a 10-min HIIE session, and blood and tissues were harvested at 1-, 4-, and 24-h post-exercise, and compared with sedentary mice. <b>Results</b>: Our findings indicate that HIIE elicits a transient systemic inflammatory response peaking at 4 h post-exercise and returning to pre-exercise levels by 24 h. Using principal component analysis, we identified a similar pattern in the mRNA profiles, with clear clusters separating sedentary groups at 1 and 4 h after acute HIIE, but not after 24 h. Although VDR mRNA follows this pattern, protein expression, as determined by Western blot and immunohistochemical analysis, reveals persistence at 24 h. As VDR was localized to the periphery of muscle fibers, we investigated and found that VDR co-localizes with PAX7 (a marker for satellite cells) and F4/80-expressing macrophages. This suggests that the observed increase in VDR expression following exercise may be attributed to ancillary cell response during muscle remodeling. <b>Conclusions</b>: Together, these results provide novel insights into the transient molecular changes occurring 1 and 4 h after HIIE, which subsequently return to baseline after 24 h. This highlights the potential of HIIE in muscle adaptation and recovery, particularly in older individuals.