A mixed-effects model of the dynamic response of muscle gene transcript expression to endurance exercise

Abstract

Altered expression of a broad range of gene transcripts after exercise reflects the specific adjustment of skeletal muscle makeup to endurance training. Towards a quantitative understanding of this molecular regulation, we aimed to build a mixed-effects model of the dynamics of co-related transcript responses to exercise. It was built on the assumption that transcript levels after exercise varied because of changes in the balance between transcript synthesis and degradation. It was applied to microarray data of 231 gene transcripts in vastus lateralis muscle of six subjects 1, 8 and 24 h after endurance exercise and 6-week training on a stationary bicycle. Cluster analysis was used to select groups of transcripts having highest co-correlation of their expression (r > 0.70): Group 1 comprised 45 transcripts including factors defining the oxidative and contractile phenotype and Group 2 included 39 transcripts mainly defined by factors found at the cell periphery and the extracellular space. Data from six subjects were pooled to filter experimental noise. The model fitted satisfactorily the responses of Group 1 (r (2) = 0.62 before and 0.85 after training, P < 0.001) and Group 2 (r (2) = 0.75 and 0.79, P < 0.001). Predicted variation in transcription rate induced by exercise yielded a difference in amplitude and time-to-peak response of gene transcripts between the two groups before training and with training in Group 2. The findings illustrate that a mixed-effects model of transcript responses to exercise is suitable to explore the regulation of muscle plasticity by training at the transcriptional level and indicate critical experiments needed to consolidate model parameters empirically.

Hypoxia refines plasticity of mitochondrial respiration to repeated muscle work

“…Adjustments of mitochondria-associated transcript and protein expression were probed and assessed for linear relationships to cellular and functional variables of oxygen metabolism. The choice of the 24-h time point to assess transcript expression after bicycle exercise was based on the established switch in COX4 isoform expression after 24 h of hypoxia exposure in culture (Fukuda et al 2007), the responsiveness of transcript expression at this time point (Busso and Fluck 2013), and the fact that at this time point the next training session would normally take place. Our study identified hypoxia-specific regulation of the COX4I2 transcript after a single bout of exercise and found that the exercise-induced changes in this transcript also correlated to exercise-induced changes in the transcript for the mitochondria-associated isoform C of lactate dehydrogenase, LDHC, and training-induced changes in volume density of subsarcolemmal mitochondria (Fig.…”

Reactive Jumps Preserve Skeletal Muscle Structure, Phenotype, and Myofiber Oxidative Capacity in Bed Rest

“…This result however is critical as pre LCFR values for both CTRL myofiber types are markedly higher than those of the JUMP group. Of note, however, is that while resistance training (Rudnick et al, 2004) and endurance training (ET) (Andersen and Henriksson, 1977;Ingjer, 1979;Hoppeler et al, 1985;Jensen et al, 2004;Schmutz et al, 2010;Busso and Fluck, 2013;Egan and Zierath, 2013) Determination of optical density of SDH marker at 660 nm (OD 660 ) in control (CTRL) (myofiber type I/II n = 6, hybrid pre n = 0 post n = 3 R + 10 n = 4) or exercise (JUMP, VL myofiber type I/II n = 6, hybrid pre n = 4, post n = 2, R + 10 = 3). The specific SDH activity (OD SDH ) was always higher in CTRL pre/post/recovery (R + 10) type I vs. type II myofibers (pre p = 0.028, post p = 0.043, recovery p = 0.014).…”

The Metabolic Response of Skeletal Muscle to Endurance Exercise Is Modified by the ACE-I/D Gene Polymorphism and Training State

“…With the repetition of exercise the consequent elevation in microvascular shear stress stimulates in conjunction with abluminal mechanical factors morphogenic adaptations and proliferation of endothelial cells in muscle capillaries (Bassett and Howley, 2000 ; Gustafsson and Kraus, 2001 ; Prior et al, 2003 ). The consequent adaptations in muscle capillarisation manifest in a typical 20–40% increase in capillary density or capillary-to-fiber ratio after a sufficiently intense and long training stimulus such as exhaustive endurance exercise when sessions are repeated 5 times per week over 4–8 weeks (Hoppeler et al, 1985 ; Schmutz et al, 2010 ; Busso and Flück, 2013 ; Egan and Zierath, 2013 ). Thereby signs of capillary remodeling in exercised muscle are already detectable 3–12 h into recovery from a single exercise session by virtue of altered muscle expression of angiogenesis-associated gene transcripts (Clifford and Hellsten, 2004 ; Egginton, 2009 ; Schmutz et al, 2010 ).…”