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.

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.

Prevention of Decompression Sickness by Novel Artificial Oxygen Carriers.

For three decades, studies have demonstrated the therapeutic efficacy of perfluorocarbon (PFC) in reducing the onset of decompression trauma. However, none of these emulsion-based preparations are accepted for therapeutic use in the western world, mainly because of severe side effects and a long organ retention time. A new development to guarantee a stable dispersion without these disadvantages is the encapsulation of PFC in nanocapsules with an albumin shell. PURPOSE: Newly designed albumin-derived perfluorocarbon-based artificial oxygen carriers (A-AOC) are used in a rodent in vivo model as a preventive therapy for decompression sickness (DCS). METHODS: Thirty-seven rats were treated with A-AOC (n = 12), albumin nanocapsules filled with neutral oil (A-O-N, n = 12), or 5% human serum albumin solution (A-0-0, n = 13) before a simulated dive. Eleven rats, injected with A-AOC, stayed at normal pressure (A-AOC surface). Clinical, laboratory, and histological evaluations were performed. RESULTS: The occurrence of DCS depended on the treatment group. A-AOC significantly reduced DCS appearance and mortality. Furthermore, a significant improvement of survival time was found (A-AOC compared with A-0-0). Histological assessment of A-AOC-dive compared with A-0-0-dive animals revealed significantly higher accumulation of macrophages, but less blood congestion in the spleen and significantly less hepatic circulatory disturbance, vacuolization, and cell damage. Compared with nondiving controls, lactate and myoglobin showed a significant increase in the A-0-0- but not in the A-AOC-dive group. CONCLUSION: Intravenous application of A-AOC was well tolerated and effective in reducing the occurrence of DCS, and animals showed significantly higher survival rates and less symptoms compared with the albumin group (A-0-0). Analysis of histological results and fast reacting plasma parameters confirmed the preventive properties of A-AOC.

Effect of personalized moderate exercise training on Wistar rats fed with a fructose enriched water.

BACKGROUND: Metabolic Syndrom has become a public health problem. It mainly results from the increased consumption of fat and sugar. In this context, the benefits of personalized moderate exercise training were investigated on a metabolic syndrome male wistar rat model food with fructose drinking water (20-25% w/v). Different markers including body weight, metabolic measurements, blood biochemistry related to metabolic syndrome complications have been evaluated. METHODS: Male Wistar rats were randomly allocated to 4 groups: control (sedentary (C, n = 8) and exercise trained (Ex, n = 8)), fructose fed (sedentary (FF, n = 8) and exercise trained fructose fed rats (ExFF, n = 10)). ExFF and Ex rats were trained at moderate intensity during the last 6 weeks of the 12 weeks-long protocol of fructose enriched water. Metabolic control was determined by measuring body weight, fasting blood glucose, HOMA 2-IR, HIRI, MISI, leptin, adiponectin, triglyceridemia and hepatic dysfunction. RESULTS: After 12 weeks of fructose enriched diet, rats displayed on elevated fasting glycaemia and insulin resistance. A reduced food intake, as well as increased body weight, total calorie intake and heart weight were also observed in FF group. Concerning biochemical markers, theoretical creatinine clearance, TG levels and ASAT/ALAT ratio were also affected, without hepatic steatosis. Six weeks of 300 min/week of moderate exercise training have significantly improved overweight, fasting glycaemia, HOMA 2-IR, MISI without modify HIRI. Exercise also decreased the plasma levels of leptin, adiponectin and the ratio leptin/adiponectin. Regarding liver function and dyslipidemia, the results were less clear as the effects of exercise and fructose-enriched water interact together, and, sometimes counteract each other. CONCLUSION: Our results indicated that positive health effects were achieved through a personalized moderate training of 300 min per week (1 h/day and 5 days/week) for 6 weeks. Therefore, regular practice of aerobic physical exercise is an essential triggering factor to attenuate MetS disorders induced by excessive fructose consumption.

Metabolic Syndrome and Hypertension Resulting from Fructose Enriched Diet in Wistar Rats.

Increased sugar consumption, especially fructose, is strongly related to the development of type 2 diabetes (T2D) and metabolic syndrome. The aim of this study was to evaluate long term effects of fructose supplementation on Wistar rats. Three-week-old male rats were randomly divided into 2 groups: control (C; n = 14) and fructose fed (FF; n = 18), with a fructose enriched drink (20-25% w/v fructose in water) for 21 weeks. Systolic blood pressure, fasting glycemia, and bodyweight were regularly measured. Glucose tolerance was evaluated three times using an oral glucose tolerance test. Insulin levels were measured concomitantly and insulin resistance markers were evaluated (HOMA 2-IR, Insulin Sensitivity Index for glycemia (ISI-gly)). Lipids profile was evaluated on plasma. This fructose supplementation resulted in the early induction of hypertension without renal failure (stable theoretical creatinine clearance) and in the progressive development of fasting hyperglycemia and insulin resistance (higher HOMA 2-IR, lower ISI-gly) without modification of glucose tolerance. FF rats presented dyslipidemia (higher plasma triglycerides) and early sign of liver malfunction (higher liver weight). Although abdominal fat weight was increased in FF rats, no significant overweight was found. In Wistar rats, 21 weeks of fructose supplementation induced a metabolic syndrome (hypertension, insulin resistance, and dyslipidemia) but not T2D.

A non-hypocholesterolemic atorvastatin treatment improves vessel elasticity by acting on elastin composition in WHHL rabbits.

BACKGROUND AND AIMS: Statins are prescribed for their preventative effects within atherosclerosis development. To our knowledge, no study focusing on very low-dose (non-hypolipidemic effect) and long-term atorvastatin treatment in vivo was available. Our aim was to assess the effect of such atorvastatin treatment on the mechanical and functional characteristics of arteries in the context of primary prevention. METHODS: An atorvastatin treatment (2.5 mg/kg/day) was tested against controls on 34 male 3 to 12 month-old WHHL rabbits. No effect on total cholesterol, triglycerides, HDL or LDL was observed. The arterial stiffness was evaluated on vigil animals by pulse wave velocity (PWV) measurement. Then, in vitro measurements were made to evaluate (1) the endothelial and vascular smooth muscle function, (2) the elasticity of the arterial wall and (3) the composition in collagen and elastin in the aorta. RESULTS: The PWV increasing observed with age in control group was canceled by treatment, creating a significance difference between groups at 12 months (5.17 ± 0.50 vs 2.14 ± 0.34 m s(-1) in control and treated groups respectively). Vasoreactivity modifications can't explain this result but maintain of elasticity with treatment in large arteries was confirm by a static tensile test. A first possible explanation is the change of wall composition with treatment, validated by the percentage of elastin at 12 months, 4.4% lower in the control group compared to the treated group (p < 0.05). CONCLUSIONS: This study shows that a non-hypocholesterolemic statin treatment could improve vessel elasticity in the atherosclerotic WHHL model. The great novelty of this work is the vessel wall composition changing associated. This first approach in animal opens the reflection on the use of these low doses in humans. This could be interesting in the context of arterial stiffening with aging, non-hyperlipidemic atherosclerosis or with cholesterol reduce by another therapy or lifestyle modification.

Progressive Induction of Type 2 Diabetes: Effects of a Reality-Like Fructose Enriched Diet in Young Wistar Rats.

PURPOSE: The aim of this study was to characterize short and medium-lasting effects of fructose supplementation on young Wistar rats. The diet was similar to actual human consumption. METHODS: Three week old male rats were randomly divided into 2 groups: control (C; n = 16), fructose fed (FF; n = 16) with a fructose enriched drink for 6 or 12 weeks. Bodyweight, fasting glycemia and systolic blood pressure were monitored. Glucose tolerance was evaluated using an oral glucose tolerance test. Insulinemia was measured concomitantly and enable us to calculate insulin resistance markers (HOMA-IR, Insulin Sensitivity Index for glycemia: ISI-gly). Blood chemistry analyses were performed. RESULTS: After six weeks of fructose supplementation, rats were not overweight but presented increased fasting glycemia, reduced glucose tolerance, and lower insulin sensitivity compared to control group. Systolic blood pressure and heart weight were also increased without any change in renal function (theoretical creatinine clearance). After twelve weeks of fructose supplementation, FF rats had increased bodyweight and presented insulin resistance (higher HOMA-IR, lower ISI-gly). Rats also presented higher heart volume and lower ASAT/ALAT ratio (presumed liver lesion). Surprisingly, the Total Cholesterol/Triglycerides ratio was increased only after six weeks of fructose supplementation, predicting a higher LDL presence and thus a higher risk of developing cardiovascular disease. This risk was no longer present after twelve weeks of a fructose enriched diet. CONCLUSION: On young Wistar rats, six weeks of fructose supplementation is sufficient to induce signs of metabolic syndrome. After twelve weeks of fructose enriched diet, rats are insulin resistant. This model enabled us to study longitudinally the early development of type 2 diabetes.

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 splenectomy on platelet activation and decompression sickness outcome in a rat model of decompression.

INTRODUCTION: Splenic platelets have been recognized to have a greater prothrombotic potential than others platelets. We studied whether platelets released by splenic contraction could influence the severity and outcome of decompression sickness (DCS) and bubble-induced platelet activation. METHODS: Sixteen, male Sprague-Dawley rats were randomly assigned to either a control or a splenectomized group. Both groups were compressed to 1,000 kPa (90 metres' sea water) for 45 min while breathing air before staged decompression (5 min at 200 kPa, 5 min at 160 kPa and 10 min at 130 kPa). The onset time of DCS symptoms and of death were recorded during a 60-min observation period post dive. Parameters measured were platelet factor 4 (PF4) for platelet activation, thiobarbituric acid reactive substances (TBARS) for oxidative stress status and Von Willebrand factor (VWf) for endothelial activation. RESULTS: There were no differences between the groups in DCS outcome or in PF4, TBARS and VWf concentrations. CONCLUSION: These results do not support that the spleen and its exchangeable platelet pool is involved in DCS pathogenesis in a rat model, invalidating the hypothesis that increased decompression-induced platelet aggregation could be influenced by splenic contraction and then play a role in DCS outcome.

Effect of tetrahydrobiopterin and exercise training on endothelium-dependent vasorelaxation in SHR

We examined whether the improvement of impaired NO-dependent vasorelaxation by exercise training could be mediated through a BH4-dependent mechanism. Male spontaneously hypertensive rats (SHR, n = 20) and Wistar-Kyoto rats (WKY, n = 20) were trained (Tr) for 9 weeks on a treadmill and compared to age-matched sedentary animals (Sed). Endothelium-dependent vasorelaxation (EDV) was assessed with acetylcholine by measuring isometric tension in rings of femoral artery precontracted with 10−5 M phenylephrine. EDV was impaired in SHR-Sed as compared to WKY-Sed (p = 0.02). Training alone improved EDV in both WKY (p = 0.01) and SHR (p = 0.0001). Moreover, EDV was not different in trained SHR than in trained WKY (p = 0.934). Pretreatment of rings with L-NAME (50 ìM) cancelled the difference in ACh-induced relaxation between all groups, suggesting that NO pathway is involved in these differences. The presence of 10−5 M BH4 in the organ bath significantly improved EDV for sedentary SHR (p = 0.030) but not WKY group (p = 0.815). Exercise training turned the beneficial effect of BH4 on SHR to impairment of ACh-induced vasorelaxation in both SHR-Tr (p = 0.01) and WKY-Tr groups (p = 0.04). These results suggest that beneficial effect of exercise training on endothelial function is due partly to a BH4-dependent mechanism in established hypertension (AU)

Effect of tetrahydrobiopterin and exercise training on endothelium-dependent vasorelaxation in SHR.

We examined whether the improvement of impaired NO-dependent vasorelaxation by exercise training could be mediated through a BH4-dependent mechanism. Male spontaneously hypertensive rats (SHR, n = 20) and Wistar-Kyoto rats (WKY, n = 20) were trained (Tr) for 9 weeks on a treadmill and compared to age-matched sedentary animals (Sed). Endothelium-dependent vasorelaxation (EDV) was assessed with acetylcholine by measuring isometric tension in rings of femoral artery precontracted with 10(-5) M phenylephrine. EDV was impaired in SHR-Sed as compared to WKY-Sed (p = 0.02). Training alone improved EDV in both WKY (p = 0.01) and SHR (p = 0.0001). Moreover, EDV was not different in trained SHR than in trained WKY (p = 0.934). Pretreatment of rings with L-NAME (50 µM) cancelled the difference in ACh-induced relaxation between all groups, suggesting that NO pathway is involved in these differences. The presence of 10(-5) M BH4 in the organ bath significantly improved EDV for sedentary SHR (p = 0.030) but not WKY group (p = 0.815). Exercise training turned the beneficial effect of BH4 on SHR to impairment of ACh-induced vasorelaxation in both SHR-Tr (p = 0.01) and WKY-Tr groups (p = 0.04). These results suggest that beneficial effect of exercise training on endothelial function is due partly to a BH4-dependent mechanism in established hypertension.

Branchial structure and hydromineral equilibrium in juvenile turbot (Scophthalmus maximus) exposed to heavy fuel oil.

This study is an attempt to go further in the comprehension of the effects of heavy fuel oil in the context of an accidental oil spill at sea. It focuses on the link between morphological and functional impacts of realistic doses of the dissolved fraction of a heavy fuel oil on fish gills. Juvenile turbot, Scophthalmus maximus were exposed to the dissolved fraction of a heavy fuel oil for 5 days and then placed 30 days in clean sea water for recovery. During the contamination period, the concentration of the 16 US EPA priority poly-aromatic hydrocarbons showed small variations around a mean value of 321.0 ± 9.1 ng l⁻¹ (mean ± SEM). The contamination induced a 64% increase in hepatic cytochrome P 450 1A (Western blot analysis). Osmolality, [Na⁺] and [Cl⁻] rapidly and significantly increased (by 14, 23 and 28% respectively) and slowly decreased to normal levels during the recovery period. At the same time, branchial histology showed decreases in the number of mucocytes (by 30%) and of chloride cells (by 95%) in the interlamellar epithelium. Therefore, it is suggested that the osmotic imbalance observed after the 5 days of exposure to the dissolved fraction of the heavy fuel oil is the consequence of the structural alteration of the gills i.e, the strong reduction of ionocyte numbers.

Evaluation of chromosomal damage by flow cytometry in turbot (Scophthalmus maximus L.) exposed to fuel oil.

Flatfishes, turbots (Scophthalmus maximus), were injected intraperitoneally with two doses of fuel oil number 2. Biliary metabolites were evaluated by fixed fluorescence to verify the efficiency of intoxication. Ethoxyresorufin-O-deethylase (EROD) activity was compared with chromosomal damage measured by flow cytometry. The analysis of biliary metabolites showed a good dose-response relation and constitutes a clear reference for the subsequent measurements. Comparing flow cytometry and EROD results, a shorter delay of response for EROD activity was obtained, but chromosomal damage was significant only after one week. The persistence of the EROD response was shorter, while the genotoxic signal still persisted after one month. The measurement of chromosomal damage allowed a good differentiation between the two tested doses. In the case of EROD activity, the results were less clear. The results suggest that within a few weeks after exposure to fuel oil number 2, the measurements of chromosomal damage by flow cytometry can be used to detect a dose-dependent genotoxic response in fish.

Motor unit properties in the soleus muscle after its distal tendon transfer to the plantaris muscle tendon in the rat.

The aim of this study was to evaluate how a modification in the mechanical conditions under which a muscle is used could induce changes in the characteristics and the spinal drive of its motor units (MU). The distal tendon of the soleus muscle of Wistar rats was transferred to the distal stump of the plantaris muscle tendon. The EMG activity of the soleus was chronically recorded for 8 weeks, every other day, during a 1-min treadmill walk. After spinal ventral root splitting, individual MU contractile properties were measured in control soleus (102 MUs) or in transposed soleus muscles after 4 weeks (41 MUs) or 8 weeks (28 MUs). Muscle/body weight ratio did not vary after transposition, nor did MU tetanic forces. A decrease in MU twitch contraction times and in their half relaxation times was observed at weeks 4 and 8. MU tension-frequency curves varied significantly after tendon transfer, becoming closer to the curves of the fast MUs of the control group. During locomotion, we observed no change in the amplitude of rectified-filtered electromyographic activity, but a significant decrease in mean burst duration and an increase in the median frequency of the power density spectrum. Tendon transposition of the soleus muscle brought about adaptations in MU contractile properties and soleus spinal control.