Altered GDF15 and FGF21 Levels in Response to Strenuous Exercise: A Study in Marathon Runners

Abstract

Background: Recreational marathon runners face strong physiological challenges. Assessment of potential biomarkers for the biological responses of runners will help to discriminate individual race responsiveness and their physiological consequences. This study sought to analyze the changes in the plasma levels of GDF15 and FGF21, novel endocrine factors related to metabolic stress, in runners following the strenuous exercise of a marathon race. Methods: Blood samples were obtained from eighteen male runners (mean ±SD, age: 41.7 ±5.0 years, BMI: 23.6 ± 1.8) 48 h before, immediately after, and 48 h after a marathon race, and from age-matched sedentary individuals. The level of GDF15, FGF21, and 38 additional biochemical and hematological parameters were determined. Results: The basal levels of GDF15 and FGF21 did not differ between runners before the race and sedentary individuals. Significant increases in the mean levels of GDF15 (4.2-fold) and FGF21 (20-fold) were found in runners immediately after the race. The magnitudes of these increases differed markedly among individuals and did not correlate with each other. The GDF15 and FGF21 levels had returned to the basal level 48 h postrace. The post-race value of GDF15 (but not FGF21) correlated positively with increased total white cell count (r = 0.50, P = 0.01) and neutrophilia (r = 0.10, P = 0.01). Conclusion: GDF15 and FGF21 are transiently increased in runners following a marathon race. The induction of GDF15 levels is associated with alterations in circulating immune cells levels.

Aerobic exercise regulates FGF21 and NLRP3 inflammasome-mediated pyroptosis and inhibits atherosclerosis in mice

“…It has been shown that serum FGF21 level was significantly increased in 14 healthy subjects who cycled for 45 min [ 35 ]. Campderrós et al [ 55 ] measured serum FGF21 in 18 male runners before and after a marathon and found that at the end of the race, the FGF21 level was 20 times higher than that before the race. However, the serum FGF21 level reduced after 36 and 12 weeks of exercise in humans and animals with obesity [ 33 , 34 ].…”

The Role of GDF15 as a Myomitokine

“…As such, exercise is one of the best therapeutic options to treat or prevent insulin resistance and type 2 diabetes [ 87 ]. We and others have shown that aerobic exercise as well as resistance exercise increase circulating GDF15 in humans [ 27 , 88 , 89 , 90 , 91 , 92 ]. Notably, GDF15 increases during and also in recovery from exercise.…”

“…For example, after 4 h of intense cycling, GDF15 increased from baseline levels of ~0.3 ng/mL to ~2 ng/mL in elite male triathletes [ 27 ]. Similarly, circulating GDF15 increased from ~0.5 ng/mL to ~1.6 ng/mL after a 130 km long cycling race in a study cohort of mostly middle-aged men [ 89 ] or from ~0.35 ng/mL to ~1 ng/mL in middle-aged male runners after completing a marathon in 3–4 h [ 88 ].…”

Refractory neutrophils and monocytes in patients with inflammatory bowel disease after repeated bouts of prolonged exercise

“…Surely, many other processes that are induced under these conditions can modulate this immune response. These are mediated by an array of soluble mediators including growth factors, cytokines, and myokines (Bay & Pedersen, 2020 ; Campderrós et al, 2020 ). Apart from these mediators, the immune response to exercise is also affected by changes in the microbiota (Adams et al, 2020 ).…”