Biology subjects

Raun, S. H.

Publications and source records attributed to Raun, S. H..

3 recordsLinked to original sources

bioRxiv2019

Housing temperature influences exercise training adaptations in mice

Exercise training is a powerful means to combat metabolic pathologies. Mice are extensively used to describe the benefits of exercise, but mild cold stress induced by housing temperatures may confound translation to humans. Thermoneutral housing is a strategy to make mice more metabolically similar to humans but its effects on exercise adaptations are unknown. Using voluntary wheel running, we show that thermoneutral housing blunted exercise-induced improvements in insulin action in muscle and adipose tissue. Moreover, thermoneutrality reduced the effects of training on energy expenditure, body composition, muscle and adipose tissue protein expressions, and the gut microbiome. The majority of these thermoneutral-dependent training adaptations could not be ascribed to a lower voluntary running volume. Thus, we conclude that organismal adaptations to exercise training in mice critically depend upon housing temperature. Our findings underscore the importance of housing temperature as an important parameter in the design and interpretation of murine exercise studies.\n\nHighlightsO_LIHousing at 30{degrees}C blunts several adaptations to exercise training in mice\nC_LIO_LIExercise-sensitive protein induction is dampened at 30{degrees}C in skeletal muscle\nC_LIO_LI30{degrees}C-housing blunts training-induced increase in insulin-stimulated glucose uptake\nC_LIO_LIGlucose tolerance is not improved by voluntary exercise training at 30{degrees}C housing\nC_LIO_LIDecreased running in 30{degrees}C housing is not due to overheating\nC_LI\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/651588v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (68K):\norg.highwire.dtl.DTLVardef@1e5b6acorg.highwire.dtl.DTLVardef@3be37corg.highwire.dtl.DTLVardef@1d3febborg.highwire.dtl.DTLVardef@f8da30_HPS_FORMAT_FIGEXP M_FIG Graphical abstract\n\nC_FIG

physiology↗

bioRxiv2019

NADPH-oxidase 2 is required for molecular adaptations to high-intensity interval training in skeletal muscle.

Objective: Reactive oxygen species (ROS) have been proposed as signaling molecules mediating exercise training adaptation, but the ROS source has remained unclear. This study aimed to investigate the requirement for NADPH oxidase (NOX)2-dependent redox changes induced by acute and long-term high-intensity interval training (HIIT) in skeletal muscle in a mouse model lacking functional NOX2 complex due to deficient p47phox (Ncf1) subunit expression (ncf1* mutation). Methods: HIIT was investigated after an acute bout of exercise and after a chronic intervention (3x week for 6 weeks) in wildtype (WT) vs. NOX2 activity-deficient (ncf1*) mice. NOX2 activation during HIIT was measured using a genetically-encoded biosensor. Immunoblotting and single-fiber staining were performed to measure classical exercise-training responsive endpoints in skeletal muscle. Results: A single bout of HIIT increased NOX2 activity measured using electroporated p47roGFP oxidation immediately after exercise but not 1h after exercise. After a 6-week of HIIT regime, improvements in maximal running capacity and some muscle training-markers responded less to HIIT in the ncf1* mice compared to WT, including superoxide dismutase (SOD)2, catalase, hexokinase II (HK II), pyruvate dehydrogenase (PDH) and protein markers of mitochondrial oxidative phosphorylation complexes. Strikingly, HIIT-training increased mitochondrial network area and decreased fragmentation in WT mice only. Conclusion: This study provided evidence that HIIT exercise activates NOX2 complex in skeletal muscle and that the presence of functional NOX2 is required for specific skeletal muscle adaptations to HIIT relating to antioxidant defense, glucose metabolism, and mitochondria.

physiology↗

bioRxiv2019

Exercise-stimulated muscle ROS production and glucose uptake requires NADPH oxidase 2

Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo but whether myocellular ROS production is stimulated by in vivo exercise to control metabolism is unclear. Here, we combined exercise in humans and mice with fluorescent dyes, genetically-encoded biosensors, and NADPH oxidase 2 (NOX2) loss-of-function models to demonstrate that NOX2 is the main source of cytosolic ROS during moderate-intensity exercise in skeletal muscle. Furthermore, two NOX2 loss-of-function mouse models lacking either p47phox or Rac1 presented striking phenotypic similarities, including greatly reduced exercise-stimulated glucose uptake and GLUT4 translocation. These findings indicate that NOX2 is a major myocellular ROS source regulating glucose transport capacity during moderate-intensity exercise.

physiology↗