Protective Effects of Regular Physical Activity: Differential Expression of , and Their Receptors in Trained and Untrained Individuals.

According to the World Health Organization (WHO), a healthy lifestyle is defined as a way of living that lowers the risk of becoming seriously ill or dying prematurely. Physical activity, as a well-known contributor to overall health, plays a vital role in supporting such a lifestyle. Exercise induces complex molecular responses that mediate both acute metabolic stress and long-term physiological adaptations. FGF21 (fibroblast growth factor 21) and GDF15 (growth differentiation factor 15) are recognized as metabolic stress markers, while their receptors play critical roles in cellular signaling. However, the differential gene expression patterns of these molecules in trained and untrained individuals following exhaustive exercise remain poorly understood. This study aimed to examine the transcriptional and protein-level responses in trained and untrained individuals performed a treadmill maximal exercise test to voluntary exhaustion. Blood samples were collected at six time points (pre-exercise, immediately post-exercise, and 0.5 h, 6 h, 24 h, and 48 h post-exercise). Gene expression of , , (fibroblast growth factor receptors), , , (β-klotho), and (glial cell line-derived neurotrophic factor receptor alpha-like) was analyzed using RT-qPCR, while plasma protein levels of FGF21 and GDF15 were quantified via ELISA. The results obtained were statistically analyzed by using Shapiro-Wilk, Mann-Whitney U, and Wilcoxon tests in Statistica 13 software. Untrained individuals demonstrated significant post-exercise upregulation of , , , and . FGF21 and GDF15 protein levels were consistently lower in trained individuals ( < 0.01), with no significant correlations between gene and protein expression. Trained individuals showed more stable expression of genes, while untrained individuals exhibited transient upregulation of genes after exercise.