The goal of the study was to determine the effects of continuous (CT) vs. intermittent (IT) training yielding identical mechanical work and training duration on skeletal muscle and cardiorespiratory adaptations in sedentary subjects. Eleven subjects (6 men and 5 women, 45 ± 3 years) were randomly assigned to either of the two 8-wk training programs in a cross-over design, separated by 12 wk of detraining. Maximal oxygen uptake (V̇o_2max) increased after both trainings (9% with CT vs. 15% with IT), whereas only IT was associated with faster V̇o₂kinetics (τ: 68.0 ± 1.6 vs. 54.9 ± 0.7 s, P < 0.05) measured during a test to exhaustion (TTE) and with improvements in maximal cardiac output (Q_max, from 18.1 ± 1.1 to 20.1 ± 1.2 l/min; P < 0.01). Skeletal muscle mitochondrial oxidative capacities ( V_max) were only increased after IT (3.3 ± 0.4 before and 4.5 ± 0.6 μmol O₂·min⁻¹·g dw⁻¹after training; P < 0.05), whereas capillary density increased after both trainings, with a two-fold higher enhancement after CT (+21 ± 1% for IT and +40 ± 3% after CT, P < 0.05). The gain of V_maxwas correlated with the gain of TTE and the gain of V̇o_2maxwith IT. The gain of Q_maxwas also correlated with the gain of VO_2max. These results suggest that fluctuations of workload and oxygen uptake during training sessions, rather than exercise duration or global energy expenditure, are key factors in improving muscle oxidative capacities. In an integrative view, IT seems optimal in maximizing both peripheral muscle and central cardiorespiratory adaptations, permitting significant functional improvement. These data support the symmorphosis concept in sedentary subjects.

Statins protect against cardiovascular-related mortality but induce skeletal muscle toxicity. To investigate mechanisms of statins, we tested the hypothesis that statins optimized cardiac mitochondrial function but impaired vulnerable skeletal muscle by inducing different level of reactive oxygen species (ROS). In atrium of patients treated with statins, ROS production was decreased and oxidative capacities were enhanced together with an extensive augmentation of mRNAs expression of peroxisome proliferator-activated receptor gamma co-activator (PGC-1) family. However, in deltoid biopsies from patients with statin-induced muscular myopathy, oxidative capacities were decreased together with ROS increase and a collapse of PGC-1 mRNA expression. Several animal and cell culture experiments were conducted and showed by using ROS scavengers that ROS production was the triggering factor responsible of atorvastatin-induced activation of mitochondrial biogenesis pathway and improvement of antioxidant capacities in heart. Conversely, in skeletal muscle, the large augmentation of ROS production following treatment induced mitochondrial impairments, and reduced mitochondrial biogenesis mechanisms. Quercetin, an antioxidant molecule, was able to counteract skeletal muscle deleterious effects of atorvastatin in rat. Our findings identify statins as a new activating factor of cardiac mitochondrial biogenesis and antioxidant capacities, and suggest the importance of ROS/PGC-1 signalling pathway as a key element in regulation of mitochondrial function in cardiac as well as skeletal muscles.

During transition from rest to exercise, metabolic reaction rates increase substantially to sustain intracellular ATP use. These metabolic demands activate several kinases that initiate signal transduction pathways which modulate transcriptional regulation of mitochondrial biogenesis. The purpose of this study was to determine whether metabolic fluctuations per se affect the signaling cascades known to regulate peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α). On two separate occasions, nine men performed a continuous (30‐min) and an intermittent exercise (30 × 1‐min intervals separated by 1‐min of recovery) at 70% of . Skeletal muscle biopsies from the vastus lateralis were taken at rest and at +0 h and +3 h after each exercise. Metabolic fluctuations that correspond to exercise‐induced variation in metabolic rates were determined by analysis of VO₂ responses. During intermittent exercise metabolic fluctuations were 2.8‐fold higher despite identical total work done to continuous exercise (317 ± 41 vs. 312 ± 56 kJ after intermittent and continuous exercise, respectively). Increased phosphorylation of AMP‐activated protein kinase (AMPK) (~2.9‐fold, P < 0.01), calcium/calmodulin‐dependent protein kinase II (CaMKII) (~2.7‐fold, P < 0.01) and p38‐mitogen‐activated protein kinase (MAPK) (~4.2‐fold, P < 0.01) occurred immediately in both exercises and to a greater extent after the intermittent exercise (condition x time interaction, P < 0.05). A single bout of intermittent exercise induces a greater activation of these signaling pathways regulating PGC‐1α when compared to a single bout of continuous exercise of matched work and intensity. Chronic adaptations to exercise on mitochondria biogenesis are yet to be investigated.