Moderate intensity continuous versus high intensity interval training: Metabolic responses of slow and fast skeletal muscles in rat.

The healthy benefits of regular physical exercise are mainly mediated by the stimulation of oxidative and antioxidant capacities in skeletal muscle. Our understanding of the cellular and molecular responses involved in these processes remain often uncomplete particularly regarding muscle typology. The main aim of the present study was to compare the effects of two types of exercise training protocol: a moderate-intensity continuous training (MICT) and a high-intensity interval training (HIIT) on metabolic processes in two muscles with different typologies: soleus and extensor digitorum longus (EDL). Training effects in male Wistar rats were studied from whole organism level (maximal aerobic speed, morphometric and systemic parameters) to muscle level (transcripts, protein contents and enzymatic activities involved in antioxidant defences, aerobic and anaerobic metabolisms). Wistar rats were randomly divided into three groups: untrained (UNTR), n = 7; MICT, n = 8; and HIIT, n = 8. Rats of the MICT and HIIT groups ran five times a week for six weeks at moderate and high intensity, respectively. HIIT improved more than MICT the endurance performance (a trend to increased maximal aerobic speed, p = 0.07) and oxidative capacities in both muscles, as determined through protein and transcript assays (AMPK-PGC-1α signalling pathway, antioxidant defences, mitochondrial functioning and dynamics). Whatever the training protocol, the genes involved in these processes were largely more significantly upregulated in soleus (slow-twitch fibres) than in EDL (fast-twitch fibres). Solely on the basis of the transcript changes, we conclude that the training protocols tested here lead to specific muscular responses.

How do exercise training variables stimulate processes related to mitochondrial biogenesis in slow and fast trout muscle fibres?

NEW FINDINGS: What is the central question of this study? Exercise is known to promote mitochondrial biogenesis in skeletal muscle, but what are the most relevant training protocols to stimulate it? What is the main finding and its importance? As in mammals, training in rainbow trout affects slow and fast muscle fibres differently. Exercise intensity, relative to volume, duration and frequency, is the most relevant training variable to stimulate the processes related to mitochondrial biogenesis in both red and white muscles. This study offers new insights into muscle fibre type-specific transcription and expression of genes involved in mitochondrial adaptations following training. ABSTRACT: Exercise is known to be a powerful way to improve health through the stimulation of mitochondrial biogenesis in skeletal muscle, which undergoes cellular and molecular adaptations. One of the current challenges in human is to define the optimal training stimulus to improve muscle performance. Fish are relevant models for exercise training physiology studies mainly because of their distinct slow and fast muscle fibres. Using rainbow trout, we investigated the effects of six different training protocols defined by manipulating specific training variables (such as exercise intensity, volume, duration and frequency), on mRNAs and some proteins related to four subsystems (AMP-activated protein kinase-peroxisome proliferator-activated receptor γ coactivator-1α signalling pathway, mitochondrial function, antioxidant defences and lactate dehydrogenase (LDH) metabolism) in both red and white muscles (RM and WM, respectively). In both muscles, high-intensity exercise stimulated more mRNA types and enzymatic activities related to mitochondrial biogenesis than moderate-intensity exercise. For volume, duration and frequency variables, we demonstrated fibre type-specific responses. Indeed, for high-intensity interval training, RM transcript levels are increased by a low training volume, but WM transcript responses are stimulated by a high training volume. Moreover, transcripts and enzymatic activities related to mitochondria and LDH show that WM tends to develop aerobic metabolism with a high training volume. For transcript stimulation, WM requires a greater duration and frequency of exercise than RM, whereas protein adaptations are efficient with a long training duration and a high frequency in both muscles.

Physiological characteristics associated with increased resistance to decompression sickness in male and female rats.

Decompression sickness (DCS) is a complex and poorly understood systemic disease with wide interindividual resistance variability. We selectively bred rats with a threefold greater resistance to DCS than standard ones. To investigate possible physiological mechanisms underlying the resistance to DCS, including sex-related differences in these mechanisms, 15 males and 15 females resistant to DCS were compared with aged-matched standard Wistar males (n = 15) and females (n = 15). None of these individuals had been previously exposed to hyperbaric treatment. Comparison of the allelic frequencies of single nucleotide polymorphisms (SNPs) showed a difference of one SNP located on the X chromosome. Compared with nonresistant rats, the neutrophil-to-lymphocyte ratio and the plasmatic activity of coagulation factor X were significantly higher in DCS-resistant individuals regardless of their sex. The maximal relaxation elicited by sodium nitroprusside was lower in DCS-resistant individuals regardless of their sex. Males but not females resistant to DCS exhibited higher neutrophil and lymphocyte counts and higher prothrombin time but lower mitochondrial basal O2 consumption and citrate synthase activity. Principal components analysis showed that two principal components discriminate the DCS-resistant males but not females from the nonresistant ones. These components were loaded with activated partial thromboplastin time, monocyte-to-lymphocyte ratio, prothrombin time, factor X, and fibrinogen for PC1 and red blood cells count and neutrophils count for PC2. In conclusion, the mechanisms that drive the resistance to DCS appear different between males and females; lower coagulation tendency and enhanced inflammatory response to decompression stress might be key for resistance in males. The involvement of these physiological adaptations in resistance to DCS must now be confirmed.NEW & NOTEWORTHY By selective breeding of individuals resistant to decompression sickness (DCS) we previously obtained a rat model of inherited resistance to this pathology. Comparison of these individuals with nonresistant animals revealed differences in leukocyte counts, coagulation, and mitochondrial and vascular functions, but not resistance to oxidative stress. This study also reveals sex-related differences in the physiological changes associated with DCS resistance. A principal components analysis of our data allowed us to discriminate DCS-resistant males from standard ones, but not females. These differences represent possible mechanisms driving resistance to DCS. Although still far from the diver, this opens a pathway to future adaptation of personalized decompression procedures for "DCS-prone" individuals.

Training protocols differently affect AMPK-PGC-1α signaling pathway and redox state in trout muscle.

Beneficial effects of physical exercise training are in part related to enhancement of muscle mitochondrial performance. The effects of two different trainings were investigated on transcripts and proteins of the AMPK-PGC-1α signaling pathway, the mitochondrial functioning (citrate synthase (CS), oxidative phosphorylation complexes, uncoupling proteins (UCP)) and the antioxidant defenses (superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase) in rainbow trout red and white skeletal muscles. One group of trouts swam for 10 days at a moderate intensity (approximately 57% Ucrit or 2.0 body lengths/s, 23.5 h/day) and another group at a high intensity (approximately 90% Ucrit or 3.2 body lengths/s, 2 h/day). In the red muscle, the increase of Cs mRNA levels was significantly correlated with the transcripts of Ampkα1, Ampkα2, Pgc-1α, the oxidative phosphorylation complexes, Ucp2α, Ucp2ß, Sod1, Sod2 and Gpx1. After 10 days of training, high intensity training (HIT) stimulates more the transcription of genes involved in this aerobic pathway than moderate intensity training (MIT) in the skeletal muscles, and mainly in the red oxidative muscle. However, no changes in CS, cytochrome c oxidase (COX) and antioxidant defenses activities and in oxidative stress marker (isoprostane plasmatic levels) were observed. The transcriptomic responses are fiber- and training-type dependent when proteins were not yet expressed after 10 days of training. As in mammals, our results suggest that HIT could promote benefit effects in fish.

Impact of a Community Pharmacist-Delivered Information Program on the Follow-up of Type-2 Diabetic Patients: A Cluster Randomized Controlled Study.

INTRODUCTION: Low-quality communication between patients and care providers and limited patient knowledge of the disease and the therapy are important factors associated with poor glycemic control in patients with type 2 diabetes. We conducted a multicenter study to determine whether structured and tailored information delivered by pharmacists to type 2 diabetic patients could improve patient treatment adherence, hemoglobin A1c (HbA1c) levels and knowledge about diabetes. METHODS: One hundred seventy-four pharmacies were randomized to deliver an educational program on diet, drug treatment, disease and complications during three 30-min interviews over a 6-month period, or to provide no intervention, to type 2 diabetic patients treated with oral antidiabetic agents. Medication adherence was assessed by measuring the medication possession ratio and diabetes control by collecting HbA1c values. Levels of patient treatment self-management and disease knowledge were assessed using self-questionnaires. RESULTS: Three hundred seventy-seven patients were analyzed. The medication possession ratio, already very high at baseline in the intervention (94.8%) and control (92.3%) groups, did not vary significantly after 6 months with no difference between the two groups. Significant decreases in HbA1c were observed in both groups at 6 months (p < 0.001) and 12 months (p < 0.01), with significantly greater changes from baseline in the intervention group than in the control group at 6 months (- 0.5% vs. - 0.2%, p = 0.0047) and 12 months (- 0.6% vs. - 0.2%, p = 0.0057). Patients in the intervention group showed greater improvement in their ability to self-manage treatment (+ 4.86 vs. + 1.58, p = 0.0014) and in the extent of their knowledge about diabetes (+ 0.6 vs. + 0.2, p < 0.01) at 6 months versus baseline compared with the control group. CONCLUSION: Tailored information provided by the pharmacist to patients with type 2 diabetes did not significantly improve the already high adherence rates, but was associated with a significant decrease in HbA1c and an improvement of patient knowledge about diabetes. TRIAL REGISTRATION: ISRCTN33776525. FUNDING: MSD France.

Long-term atorvastatin treatment decreases heart maximal oxygen consumption and its vulnerability to in vitro oxidative stress in Watanabe heritable hyperlipidemic rabbit.

Statins are currently used in prevention of cardiovascular diseases in high-risk populations, and could be considered in primary prevention. However, few studies are available on the long-term effects of low doses of statins, especially on mitochondrial function and reactive oxygen species (ROS) metabolism at cardiac level. This study aimed to determine potential effects of a long-term atorvastatin treatment, at low-dose concentration, on the myocardium mitochondrial respiration. Thirty-four Watanabe rabbits were treated or not with atorvastatin (2.5 mg·kg-1·day-1) from the age of 3 to 12 months. Every 3 months, proton leak, basal (V0), and maximal (Vmax) mitochondrial respiration on cardiac permeabilized fibers were measured. Additionally, the vulnerability to ROS, cardiac enzymatic antioxidant defenses, and oxidative damage (lipoperoxidation) were analyzed. Proton leak increased over the duration of the experiment (up to 60% from Vmax at 12 months). Moreover, the statin treatment induced a decrease of Vmax and a decrease of ROS susceptibility of cardiac mitochondria. However, the lipoperoxidation and the antioxidant defenses were not dependent on the presence of statin treatment, or on its duration. This is the first study showing a protective effect of long-term statins treatment against the ROS susceptibility in the cardiac muscle.

Gender-dependent differences of mitochondrial function and oxidative stress in rat skeletal muscle at rest and after exercise training.

OBJECTIVE: This study investigated gender-dependent differences of mitochondrial function and sensitivity to in vitro ROS exposure in rat skeletal muscle at rest and after exercise training. METHODS: Wistar rats underwent running training for 6 weeks. In vitro measurements of hydroxyl radical production, oxygen consumption (under basal and maximal respiration conditions) and ATP production were made on permeabilized fibers. Mitochondrial function was examined after exposure and non-exposure to an in vitro generator system of reactive oxygen species (ROS). Antioxidant enzyme activities and malondialdehyde (MDA) content were also determined. RESULTS: Compared with sedentary males, females showed a greater resistance of mitochondrial function (oxygen consumption and ATP production) to ROS exposure, and lower MDA content and antioxidant enzyme activities. The training protocol had more beneficial effects in males than females with regard to ROS production and oxidative stress. In contrast to male rats, the susceptibility of mitochondrial function to ROS exposure in trained females was unchanged. DISCUSSION: Exercise training improves mitochondrial function oxidative capacities in both male and female rats, but is more pronounced in males as a result of different mechanisms. The resistance of mitochondrial function to in vitro oxidative stress exposure and the antioxidant responses are gender- and training-dependent, and may be related to the protective effects of estrogen.

Silvering and swimming effects on aerobic metabolism and reactive oxygen species in the European eel.

Silvering, the last metamorphosis in the eel life cycle induces morphological and physiological modifications in yellow eels (sedentary stage). It pre-adapts them to cope with the extreme conditions they will encounter during their 6000-km spawning migration. A previous study showed that silver eels are able to cope with reactive oxygen species (ROS) over-production linked to an increase in aerobic metabolism during sustained swimming, but the question remains as to whether this mechanism is associated with silvering. A sustained swimming session decreased red muscle in vitro mitochondrial oxygen consumption (MO2) but increased ROS production in both eel stages. The swimming exercise used here was perhaps too intense to induce a stimulation of mitochondrial function or biogenesis even when antioxidant enzyme activities were unchanged. Pro-oxidant/antioxidant imbalance by lipid peroxidation increased in yellow but significantly decreased in silver eels. The silvering process therefore appears to allow a pre-adaptation of red muscle radical metabolism to the demands of spawning migration.

Effect of exercise training on oxidative stress and mitochondrial function in rat heart and gastrocnemius muscle.

OBJECTIVE: This study aimed to explore the effect of endurance training on oxidative parameters and mitochondrial function in gastrocnemius and heart muscle. METHODS: Male Wistar rats were trained by running for 6 weeks. In vitro measurements of the rates of hydroxyl radical ((•)OH) production, oxygen consumption (in either the absence, basal rate (V0), or the presence, maximal rate (Vmax), of adenosine diphosphate), and adenosine triphosphate (ATP) production were made simultaneously in permeabilized fibers. The mitochondrial function was explored after exposure or non-exposure to an in vitro generator system of reactive oxygen species (ROS). RESULTS: Vmax was not affected by training, but V0 decreased. In conditions of maximal mitochondrial functioning, an increase in ATP rate and a decrease in (•)OH production occurred simultaneously. In vitro ROS exposure disturbed mitochondrial function, but training modified the vulnerability of Vmax and ATP rate to ROS in different ways. DISCUSSION: We hypothesize that the part of Vmax devoted to proton leakage was decreased in trained rats, consequently improving ATP synthesis. The data suggest that, after training, there is more efficient use of electrons in respiratory chain energy production, rather than a greater ROS scavenging capacity.

Effect of induced mild hypothermia on two pro-inflammatory cytokines and oxidative parameters during experimental acute sepsis.

This study aimed to determine the effect of induced mild hypothermia (34°C) on the production of two cytokines (interleukin (IL-6) and tumor necrosis factor (TNF)alpha) and reactive nitrogen and oxygen species in plasma and the heart of acutely septic rats. After anesthesia and in conditions of normothermia (38°C) or mild hypothermia (34°C), acute sepsis was induced by cecal ligation and perforation. For each temperature three groups were formed: (1) baseline (blood sample collected at T0 hour), (2) sham (blood sample at T4 hours) and (3) septic (blood sample at T4 hours). At either temperature sepsis induced a significant increase in plasma IL-6, TNF-alpha and HO• concentration, compared with the sham groups (P≤0.016). Compared with the normothermic septic group, septic rats exposed to mild hypothermia showed a mild decrease in TNF-alpha concentration (104±50 pg/ml vs. 215±114 pg/ml; P>0.05) and a significant decrease in IL-6 (1131±402 pg/ml vs. 2494±691 pg/ml, P=0.038). At either temperature sepsis induced no enhancement within the heart of lipoperoxidation (malondialdehyde content) or antioxidant activities (superoxide dismutase and catalase). In conclusion, during acute sepsis, induced mild hypothermia appears to reduce some pro-inflammatory and oxidative responses. This may, in part, explain the beneficial effect of hypothermia on survival duration of septic rats.

In vitro aerobic and anaerobic muscle capacities in the European eel, Anguilla anguilla: effects of a swimming session.

In order to have a general view of metabolic requirements during swimming, in vitro aerobic and anaerobic fluxes were measured in red and white muscles from silver eels and yellow eels which differ in activity levels and nutritional states. These measurements were performed in control eels and after a 4 day swimming session (70% U(crit) in yellow eels, 80% U(crit) in silver eels). A swimming session significantly increases U(crit) from 12% to 18%, depending on the stage, with a significantly higher in vitro energy cost during the yellow stage at the muscle level. In vitro, the swimming session brings about a gain in anaerobic capacities rather than in aerobic ones. Some in vivo hypotheses are proposed.

Effect of exercise training on respiration and reactive oxygen species metabolism in eel red muscle.

This paper deals with the effects of exercise training on oxygen consumption (MO(2)) and ROS metabolism in the red muscle of trained and untrained female silver eels. Their critical swimming speed (U(crit)) was determined before and after a 4-day training (10h of swimming at 70% of U(crit) and 14 h at 50%, every day). The U(crit) of trained eels increased significantly (by about 7%). The in vitro MO(2) and ROS production by the red fibres were higher (not significant) in trained than in untrained eels, but the ROS production/MO(2) ratio was alike in both groups. The antioxidant-enzyme activities and lipoperoxidation index in trained eels were both lower than those of the untrained ones. These biochemical changes related to the increase in U(crit) suggest that such a training session could maintained or even increased aerobic power of the red muscle without deleterious impact by ROS. These regulations could play a role in the eel's swimming performance efficiency.

In vitro effect of hydrostatic pressure exposure on hydroxyl radical production in fish red muscle.

The effects of hydrostatic pressure on reactive oxygen species (ROS) production have been studied in vitro on fish red muscle fibres. In the eel, Anguilla anguilla, previous studies have shown that hydrostatic pressure acclimatization improves oxidative phosphorylation efficiency together with a supposed concomitant decrease in electron leak and ROS production. In order to test the hypothesis of an electron leak decrease under pressure, hydroxyl radical (HO*) production and oxygen consumption were measured on fish red muscle fibres directly exposed to hydrostatic pressure. Experiments were performed under two conditions--atmospheric pressure and hydrostatic pressure (16.1 MPa)--on eel and trout (which exhibit low- and high-pressure sensitivity, respectively). This work has permitted, first, the validation of an indirect HO* measurement (in vitro) on fish red muscle and the documentation of reference values for fish. Second, at atmospheric pressure, results show higher oxygen consumption for trout (+40%) than for eel which is accompanied by higher HO* production (+90%); in addition, both species present a positive relationship between HO* production and oxygen consumption. Hydrostatic pressure exposure reverses this relationship for eel but not for trout. These preliminary results only partially verify the proposed hypothesis and further experiments are needed.

Is the silvering process similar to the effects of pressure acclimatization on yellow eels?

To reproduce eels need to migrate over 6000 km and at pressure but before this migration they metamorphose into silver eels (silvering). The question raised in this study is to determine whether and how the silvering process contributes to pressure resistance. As migration represents a long swimming activity mainly performed with slow muscles, the red muscle energetics of pressure exposed silver eels was studied. By comparing these results to what has already been shown in yellow eels, we point out that the effects of the silvering process on pressure resistance are similar to the effects of pressure acclimatization in yellow eels. As previously shown, success of pressure acclimatization depends on membrane fluidity, but we raise the hypothesis that the high-pressure resistance of silver eels is due to more fluid membranes.