Abstract
Physical activity is an important contributor to muscle adaptation and metabolic health. Growth differentiation factor 15 (GDF15) is established as cellular and nutritional stress-induced cytokine but its physiological role in response to active lifestyle or acute exercise is unknown. Here, we investigated the metabolic phenotype and circulating GDF15 levels in lean and obese male C57Bl/6J mice with long-term voluntary wheel running (VWR) intervention. Additionally, treadmill running capacity and exercise-induced muscle gene expression was examined in GDF15-ablated mice. Active lifestyle mimic via VWR improved treadmill running performance and, in obese mice, also metabolic phenotype. The post-exercise induction of skeletal muscle transcriptional stress markers was reduced by VWR. Skeletal muscle GDF15 gene expression was very low and only transiently increased post-exercise in sedentary but not in active mice. Plasma GDF15 levels were only marginally affected by chronic or acute exercise. In obese mice, VWR reduced GDF15 gene expression in different tissues but did not reverse elevated plasma GDF15. Genetic ablation of GDF15 had no effect on exercise performance but augmented the post exercise expression of transcriptional exercise stress markers (Atf3, Atf6, and Xbp1s) in skeletal muscle. We conclude that skeletal muscle does not contribute to circulating GDF15 in mice, but muscle GDF15 might play a protective role in the exercise stress response.
Highlights
Physical activity is an important contributor to muscle adaptation and metabolic health
In order to assess the potential role of Growth differentiation factor 15 (GDF15) during exercise adaptation, we provided wild-type (WT) C57BL/6J mice at 7 wks of age with a running wheel and compared them with mice provided with no running wheel
This resulted in a significantly improved endurance exercise capacity which was 2.7 fold increased by voluntary wheel running (VWR) by week 15 (Fig. 1e) confirming previous data obtained with a comparable study setup[19,20]
Summary
Physical activity is an important contributor to muscle adaptation and metabolic health. Active lifestyle mimic via VWR improved treadmill running performance and, in obese mice, metabolic phenotype. Skeletal muscle GDF15 gene expression was very low and only transiently increased post-exercise in sedentary but not in active mice. An acute bout of strenuous exercise imposes a severe physiological stress resulting in the activation of specific signaling pathways regulating exercise-induced gene expression and protein synthesis[5]. Skeletal muscle adaptations to exercise training are the result of repeated, transient bursts in mRNA expression during each exercise bout that have a cumulative effect and lead to increases in transcription of nuclear- and mitochondrial-encoded proteins[6]. We investigated the acute skeletal muscle transcriptional response to an exhaustive exercise bout in sedentary and active mice, and the effect of VWR on circulating GDF15. Exercise capacity and post exercise muscle gene expression were examined in GDF15-ablated mice
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