Histone deacetylase activity modulates exercise-induced skeletal muscle plasticity in zebrafish (Danio rerio).

Aerobic exercise has a positive impact on animals by enhancing skeletal muscle function and locomotor performance. Responses of skeletal muscle to exercise involve changes in energy metabolism, calcium handling, and the composition of contractile protein isoforms, which together influence contractile properties. Histone deacetylases (HDAC) can cause short-term changes in gene expression and may thereby mediate plasticity in contractile properties of skeletal muscle in response to exercise. The aim of this project was to determine (in zebrafish, Danio rerio) the traits that mediate interindividual differences in sustained and sprint performance and to determine whether inhibiting class I and II HDACs mediates exercise-induced changes in these traits. High sustained performers had greater aerobic metabolic capacity [citrate synthase (CS) activity], calcium handling capacity [sarco/endoplasmic reticulum ATPase (SERCA) activity], and slow contractile protein concentration [slow myosin heavy chain (MHC)] compared with low performers. High sprint performers had lower CS activity and slow MHC concentrations compared with low performers, but there were no significant differences in lactate dehydrogenase activity or fast MHC concentrations. Four weeks of aerobic exercise training increased sustained performance, CS activity, SERCA activity, and slow MHC concentration. Inhibiting class I and II HDACs increased slow MHC concentration in untrained fish but not in trained fish. However, inhibiting HDACs reduced SERCA activity, which was paralleled by a reduction in sustained and sprint performance. The regulation of muscle phenotypes by HDACs could be a mechanism underlying the adaptation of sustained locomotor performance to different environmental conditions, and may therefore be of therapeutic and ecological significance.

Histone deacetylase activity mediates thermal plasticity in zebrafish (Danio rerio).

Regulatory mechanisms underlying thermal plasticity determine its evolution and potential to confer resilience to climate change. Here we show that class I and II histone deacetylases (HDAC) mediated thermal plasticity globally by shifting metabolomic profiles of cold acclimated zebrafish (Danio rerio) away from warm acclimated animals. HDAC activity promoted swimming performance, but reduced slow and fast myosin heavy chain content in cardiac and skeletal muscle. HDAC increased sarco-endoplasmic reticulum ATPase activity in cold-acclimated fish but not in warm-acclimated animals, and it promoted cardiac function (heart rate and relative stroke volume) in cold but not in warm-acclimated animals. HDAC are an evolutionarily ancient group of proteins, and our data show that they mediate the capacity for thermal plasticity, although the actual manifestation of plasticity is likely to be determined by interactions with other regulators such as AMP-activated protein kinase and thyroid hormone.

Zebrafish (Danio rerio) as a Model for Sprint Exercise Training.

Sprint performance is important ecologically and physiologically, and it can influence fitness by determining outcomes of predator-prey relationships, for example, and it can confer substantial human health benefits. In this article we test whether zebrafish (Danio rerio) are a suitable model to test hypotheses about the effects and consequences of sprint exercise training, and the physiological underpinnings of sprint performance. We show that stage 3 c-starts that capture the initial escape response of fish lasting <1 s were repeatable within individuals. In addition, somewhat longer constant acceleration protocols lasting 10 s (U10s) or 30 s (U30s) were highly repeatable within individuals over 3, 6, and 23 days. C-starts within individuals were not correlated with either U10s or U30s, indicating that these measures reflect different physiological aspects of sprinting. Stage 3 c-starts and U10s responded positively to sprint exercise training. Our exercise training protocol (5 × 10 s sprints with 5-min rest periods on 4 days per week for 3 weeks) was based on the human sporting literature, and together, our results indicate that zebrafish are a good model to assess the physiological and behavioral consequences of sprint exercise training.