New approach for weight reduction by a combination of diet, light resistance exercise and the timing of ingesting a protein supplement.

We have reported that ingesting a meal immediately after exercise increased skeletal muscle accretion and less adipose tissue accumulation in rats employed in a 10 week resistance exercise program. We hypothesized that a possible increase in the resting metabolic rate (RMR) as a result of the larger skeletal muscle mass might be responsible for the less adipose deposition. Therefore, the effect of the timing of a protein supplement after resistance exercise on body composition and the RMR was investigated in 17 slightly overweight men. The subjects participated in a 12-week weight reduction program consisting of mild energy restriction (17% energy intake reduction) and a light resistance exercise using a pair of dumbbells (3-5 kg). The subjects were assigned to two groups. Group S ingested a protein supplement (10 g protein, 7 g carbohydrate, 3.3 g fat and one-third of recommended daily allowance (RDA) of vitamins and minerals) immediately after exercise. Group C did not ingest the supplement. Daily intake of both energy and protein was equal between the two groups and the protein intake met the RDA. After 12 weeks, the bodyweight, skinfold thickness, girth of waist and hip and percentage bodyfat significantly decreased in the both groups, however, no significant differences were observed between the groups. The fat-free mass significantly decreased in C, whereas its decrease in S was not significant. The RMR and post-meal total energy output significantly increased in S, while these variables did not change in C. In addition, the urinary nitrogen excretion tended to increase in C but not in S. These results suggest that the RMR increase observed in S might be associated with an increase in body protein synthesis.

Protein turnover and thermogenesis in response to high-protein and high-carbohydrate feeding in men.

The rates of energy expenditure and wholebody protein turnover were determined during a 9-h period in a group of seven men while they received hourly isocaloric meals of high-protein (HP) or high-carbohydrate (HC) content. Their responses to feeding were compared with those to a short period of fasting (15-24 h). The 9-h thermic response to the repeated feeding of HP meals was found to be greater than that to the HC meals (9.6 +/- 0.6% vs 5.7 +/- 0.4% of the energy intake, respectively, means +/- SEM, p less than 0.01). The rate of whole-body nitrogen turnover over 9 h increased from 17.6 +/- 2.2 g on the fasting day to 27.4 +/- 1.4 g during HC feeding (NS) and there was a further increase to 58.2 +/- 5.3 g resulting from HP feeding (p less than 0.001). By using theoretical estimates (based upon ATP requirements) of the metabolic cost of protein synthesis, 36 +/- 9% of the thermic response to HC feeding and 68 +/- 3% of the response to HP feeding could be accounted for by the increases in protein synthesis compared with the fasting state.

Exposure to solute stress affects genome-wide expression but not the polycyclic aromatic hydrocarbon-degrading activity of Sphingomonas sp. strain LH128 in biofilms.

Members of the genus Sphingomonas are important catalysts for removal of polycyclic aromatic hydrocarbons (PAHs) in soil, but their activity can be affected by various stress factors. This study examines the physiological and genome-wide transcription response of the phenanthrene-degrading Sphingomonas sp. strain LH128 in biofilms to solute stress (invoked by 450 mM NaCl solution), either as an acute (4-h) or a chronic (3-day) exposure. The degree of membrane fatty acid saturation was increased as a response to chronic stress. Oxygen consumption in the biofilms and phenanthrene mineralization activities of biofilm cells were, however, not significantly affected after imposing either acute or chronic stress. This finding was in agreement with the transcriptomic data, since genes involved in PAH degradation were not differentially expressed in stressed conditions compared to nonstressed conditions. The transcriptomic data suggest that LH128 adapts to NaCl stress by (i) increasing the expression of genes coping with osmolytic and ionic stress such as biosynthesis of compatible solutes and regulation of ion homeostasis, (ii) increasing the expression of genes involved in general stress response, (iii) changing the expression of general and specific regulatory functions, and (iv) decreasing the expression of protein synthesis such as proteins involved in motility. Differences in gene expression between cells under acute and chronic stress suggest that LH128 goes through changes in genome-wide expression to fully adapt to NaCl stress, without significantly changing phenanthrene degrading activity.

Inhibition of Na(+)-K(+)-ATPase by digoxin and its relation with energy expenditure and nutrient oxidation rate.

This study investigates the effects of digoxin, an inhibitor of the Na+ pump (Na(+)-K(+)-ATPase), on resting metabolic rate (RMR), respiratory quotient (RQ), and nutrient oxidation rate. Twelve healthy male subjects followed a double-blind protocol design and received either 1 mg/day digoxin or a placebo 2 days before indirect calorimetry measurements. Digoxin induced a 0.22 +/- 0.07 kJ/min or 3.8 +/- 1.5% (mean +/- SE, P = 0.01) decrease in RMR and a 0.40 +/- 0.13 kJ/min (P = 0.01) decrease in fat oxidation rate, whereas carbohydrate and protein oxidation rates did not change significantly. A dose-response relationship between serum digoxin and RQ was observed. These results suggest that digoxin reduces not only RMR but also fat oxidation rate by mechanisms that remain to be elucidated. Because a linkage and an association between genes coding the Na(+)-K(+)-ATPase and the RQ have been previously observed, the present demonstration of an effect of Na(+)-K(+)-ATPase inhibition on fat oxidation rate strengthens the concept that the activity of this enzyme may play a role in body weight regulation.

Synaptic plasticity and the Warburg effect.

Functional brain imaging studies show that in certain brain regions glucose utilization exceeds oxygen consumption, indicating the predominance of aerobic glycolysis. In this issue, Goyal et al. (2014) report that this metabolic profile is associated with an enrichment in the expression of genes involved in synaptic plasticity and remodeling processes.

Exercise dose and insulin sensitivity: relevance for diabetes prevention.

PURPOSE: Exercise improves insulin resistance and is a first line for the prevention and treatment of type 2 diabetes. The extent, however, to which these responses are dose dependent is not known. The purpose of this study was to examine whether exercise dose was associated with improvements in insulin sensitivity after 4 months of exercise training in previously sedentary adults. METHODS: Fifty-five healthy volunteers participated in a 16-wk supervised endurance exercise intervention with a pre/postintervention design. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp, peak oxygen uptake by a graded exercise test, and body composition by dual-energy x-ray absorptiometry. The exercise intervention consisted of three to five sessions per week with a minimum of three sessions supervised. A ramped exercise prescription protocol was used to achieve 75% of peak HR for 45 min per session. Exercise dose, expressed as average kilocalories expended per week, was computed as the product of exercise intensity, duration and frequency. RESULTS: Improved insulin sensitivity was significantly related to exercise dose in a graded dose-response relationship. No evidence of threshold or maximal dose-response effect was observed. Age and gender did not influence this dose-response relationship. Exercise intensity was also significantly related to improvements in insulin sensitivity, whereas frequency was not. CONCLUSIONS: This study identifies a graded dose-response relationship between exercise dose and improvements in insulin sensitivity. The implication of this observation is of importance for the adaptation of exercise prescription in clinical situations.

The biology of cancer stem cells : part 1: nuclear translocation of CD44 : part 2: IMP2 in glioblastoma cancer stem cells

SummaryCancer stem cells (CSC) are poorly differentiated, slowly proliferating cells, with high tumorigenic potential. Some of these cells, as it has been shown in leukemia, evade chemo- and radiotherapy and recapitulate the tumor composed of CSC and their highly proliferative progeny. Therefore, understanding the molecular biology of those cells is crucial for improvement of currently used anti-cancer therapies.This work is composed of two CSC-related projects. The first deals with CD44, a frequently used marker of CSC; the second involves Imp2 and its role in CSC bioenergetics. PART 1. CD44 is a multifunctional transmembrane protein involved in migration, homing, adhesion, proliferation and survival. It is overexpressed in many cancers and its levels are correlated with poor prognosis. CD44 is also highly expressed by CSC and in many malignancies it is used for CSC isolation.In the present work full-lenght CD44 nuclear localization was studied, including the mechanism of nuclear translocation and its functional role in the nucleus. Full-length CD44 can be found in nuclei of various cell types, regardless of their tumorigenic potential. For nuclear localization, CD44 needs to be first inserted into the cell membrane, from which it is transported via the endocytic pathway. Upon binding to transportinl it is translocated to the nucleus. The nuclear localization signal recognized by transportinl has been determined as the first 20 amino acids of the membrane proximal intracellular domain. Nuclear export of CD44 is facilitated by exportin Crml. Investigation of the function of nuclear CD44 revealed its implication in de novo RNA synthesis.PART 2. Glioblastoma multiforme is the most aggressive and most frequent brain malignancy. It was one of the first solid tumors from which CSC have been isolated. Based on the similarity between GBM CSC and normal stem cells expression of an oncofetal mRNA binding protein Imp2 has been investigated.Imp2 is absent in normal brain as well as in low grade gliomas, but is expressed in over 75% GBM cases and its expression is higher in CSC compared to their more differentiated counterparts. Analysis of mRNA transcripts bound by Imp2 and its protein interactors revealed that in GBM CSC Imp2 may be implicated in mitochondrial metabolism. Indeed, shRNA mediated silencing of protein expression led to decreased mitochondrial activity, decreased oxygen consumption and decreased activity of respiratory chain protein complex I. Moreover, lack of Imp2 severely affected self-renewal and tumorigenicity of GBM CSC. Experimental evidence suggest that GBM CSC depend on mitochondrial oxidative phosphorylation as an energy producing pathway and that Imp2 is a novel regulator of this pathway.RésuméLes cellules cancéreuses souches sont des cellules peu différentiées, à proliferation lente et hautement tumorigénique. Ces cellules sont radio-chimio résistantes et sont capable reformer la tumeur dans sont intégralité, reproduisant l'hétérogénéité cellulaire présent dans la tumeur d'origine. Pour améliorer les therapies antitumorales actuelles il est crucial de comprendre les mécanismes moléculaires qui caractérisent cette sous-population de cellules hautement malignes.Ce travail de thèse se compose de deux projets s'articulant autour du même axe :Le CD44 est une protéine multifonctionnelle et transmembranaire très souvent utilisée comme marqueur de cellules souches tumorales dans différents cancers. Elle est impliquée dans la migration, l'adhésion, la prolifération et la survie des cellules. Lors de ce travail de recherche, nous nous sommes intéressés à la localisation cellulaire du CD44, ainsi qu'aux mécanismes permettant sa translocation nucléaire. En effet, bien que principalement décrit comme un récepteur de surface transmembranaire, le CD44 sous sa forme entière, non clivée en peptides, peut également être observé à l'intérieur du noyau de diverses cellules, quel que soit leur potentiel tumorigénique. Pour passer ainsi d'un compartiment cellulaire à un autre, le CD44 doit d'abord être inséré dans la membrane plasmique, d'où il est transporté par endocytose jusqu'à l'intérieur du cytoplasme. La transportai permet ensuite la translocation nucléaire du CD44 via une « séquence signal » contenue dans les 20 acides aminés du domaine cytoplasmique qui bordent la membrane. A l'inverse, le CD44 est exporté du noyau grâce à l'exportin Crml. En plus des mécanismes décrits ci-dessus, cette étude a également mis en évidence l'implication du CD44 dans la synthèse des ARN, d'où sa présence dans le noyau.Le glioblastome est la plus maligne et la plus fréquente des tumeurs cérébrales. Dans ce second projet de recherche, le rôle de IMP2 dans les cellules souches tumorales de glioblastomes a été étudié. La présence de cette protéine oncofoetale a d'abord été mise en évidence dans 75% des cas les plus agressifs des gliomes (grade IV, appelés glioblastomes), tandis qu'elle n'est pas exprimée dans les grades I à III de ces tumeurs, ni dans le cerveau sain. De plus, IMP2 est apparue comme étant davantage exprimée dans les cellules souches tumorales que dans les cellules déjà différenciées. La baisse de l'expression de IMP2 au moyen de shRNA a résulté en une diminution de l'activité mitochondriale, en une réduction de la consommation d'oxygène ainsi qu'en une baisse de l'activité du complexe respiratoire I.L'inhibition de IMP2 a également affecté la capacité de renouvellement de la population des cellules souches tumorales ainsi que leur aptitude à former des tumeurs.Lors de ce travail de thèse, une nouvelle fonction d'un marqueur de cellules souches tumorales a été mise en évidence, ainsi qu'un lien important entre la bioénergétique de ces cellules et l'expression d'une protéine oncofoetale.

Whole-body vibration training: metabolic cost of synchronous, side-alternating or no vibrations.

Whole-body vibration training improves strength and can increase maximal oxygen consumption ([·V]O(2max)). No study has compared the metabolic demand of synchronous and side-alternating whole-body vibration. We measured [·V]O₂ and heart rate during a typical synchronous or side-alternating whole-body vibration session in 10 young female sedentary participants. The 20-min session consisted of three sets of six 45-s exercises, with 15 s recovery between exercises. Three conditions were randomly tested on separate days: synchronous at 35 Hz and 4 mm amplitude, side-alternating at 26 Hz and 7.5 mm amplitude (peak acceleration matched at 20 g in both vibration conditions), and no vibrations. Mean [·V]O₂ (expressed as %[·V]O(2max)) did not differ between conditions: 29.7 ± 4.2%, 32.4 ± 6.5%, and 28.7 ± 6.7% for synchronous, side-alternating, and no vibrations respectively (P = 0.103). Mean heart rate (% maximal heart rate) was 65.6 ± 7.3%, 69.8 ± 7.9%, and 64.7 ± 5.6% for synchronous, side-alternating, and no vibrations respectively, with the side-alternating vibrations being significantly higher (P = 0.019). When analysing changes over exercise sessions, mean [·V]O₂ was higher for side-alternating (P < 0.001) than for synchronous and no vibrations. In conclusion, side-alternating whole-body vibration elicits higher heart rate responses than synchronous or no vibrations, and could elevate [·V]O₂, provided the session lasts more than 20 min.

Energy expenditure and postprandial thermogenesis in obese women before and after weight loss.

In six young obese women (mean weight 85 +/- 3 kg) with a childhood history of obesity, and in six young nonobese women (mean weight 55 +/- 2 kg), the energy expenditure was measured during 24 h in a respiratory chamber with a maintenance energy intake. The next day, the thermogenic response to a mixed meal was investigated by using an open circuit indirect calorimetry hood system. In addition, five of the same obese women were similarly studied after a mean weight loss of 12.1 kg (14% of initial body weight) consecutive to an 11-wk hypocaloric diet (protein-supplemented modified fast). Expressed in absolute terms, the total 24 h and basal energy expenditures were found to be significantly greater in the obese (2208 +/- 105 and 1661 +/- 56 kcal/24 h, respectively) than in the controls (1746 +/- 61 and 1230 +/- 40 kcal/24 h, respectively). After weight loss, both the total 24-h and the basal energy expenditures were significantly reduced (2009 +/- 99 kcal/24 h and 1423 +/- 43 kcal/24 h respectively), but both values were still greater than that of the control subjects. The thermogenic response to the mixed meal (a liquid diet containing 17, 54, and 29% as protein, carbohydrate, and lipid calories, respectively, and an energy level determined to cover 60% of the basal energy expenditure computed for 24 h) was found to be significantly reduced in the obese as compared to controls (ie, 7.6 +/- 0.4% versus 9.5 +/- 0.4% of the energy content of the load, respectively, p less than 0.025). After weight loss, the postprandial thermogenesis of the obese was still markedly reduced (ie, 6.2 +/- 0.8%). Both before and after weight loss, the relative increase in diurnal urinary norepinephrine excretion was found to be lower in the obese than in controls, when compared to the nocturnal values. These results show that the greater 24 h energy expenditure of obese women is entirely due to their higher basal metabolic rate. The lower thermogenic response to the meal in the obese supports the concept of a thermogenic defect which can favor energy gain; furthermore, the unchanged response after weight loss in the obese suggests that the thermogenic defect may be a cause rather than a consequence of obesity.

Postprandial thermogenesis at rest and during exercise in elderly men ingesting two levels of protein.

Seven elderly male subjects (69 +/- 3 yr, 67.8 +/- 9.2 kg, 24.5 +/- 3.6% body fat) lived for 12 consecutive weeks in a metabolic unit and maintained their weight with two different diets fed for 6 weeks each: Diet A, consisted of their habitual protein intake as determined on the outside by a dietary record (mean +/- SD, 1.12 +/- 0.22 g/kg d). Diet B was an isocaloric diet with reduced protein intake (70 mgN/kg d, i.e., 0.44 g protein/kg d) at the level of physiological protein requirement [7]. After 3 weeks on each diet, the thermogenic response to single meals A and B containing 38% of weight maintenance energy for each subject (731-994 kcal) was studied by indirect calorimetry under two situations: (1) at rest over a 4 hr period and (2) during graded exercise on a bicycle ergometer at four stepwise workloads (0,80, 200, and 300 kg/min). A postabsorptive control exercise was also performed in order to assess the net effect of the meal during exercise. Eating alone increased the energy expenditure by +0.18 +/- 0.07 kcal/min with meal A and +0.13 +/- 0.06 kcal/min with meal B. There was a positive correlation (r = 0.84, p less than 0.01) between the % energy derived from protein and the thermogenic response expressed as % of the energy content of test meal. Exercise failed to influence the thermogenic response to meals since the overall net increase in energy expenditure induced by the meals while exercising was not different from that obtained at rest: +0.22 +/- 0.17 kcal/min and +0.15 +/- 0.13 kcal/min with meal A and meal B, respectively. This study failed to show any interaction between exercise and postprandial thermogenesis in elderly individuals.

Reproducibility of Fatmax and Fat Oxidation Rates during Exercise in Recreationally Trained Males.

Aerobic exercise training performed at the intensity eliciting maximal fat oxidation (Fatmax) has been shown to improve the metabolic profile of obese patients. However, limited information is available on the reproducibility of Fatmax and related physiological measures. The aim of this study was to assess the intra-individual variability of: a) Fatmax measurements determined using three different data analysis approaches and b) fat and carbohydrate oxidation rates at rest and at each stage of an individualized graded test. Fifteen healthy males [body mass index 23.1±0.6 kg/m2, maximal oxygen consumption ([Formula: see text]) 52.0±2.0 ml/kg/min] completed a maximal test and two identical submaximal incremental tests on ergocycle (30-min rest followed by 5-min stages with increments of 7.5% of the maximal power output). Fat and carbohydrate oxidation rates were determined using indirect calorimetry. Fatmax was determined with three approaches: the sine model (SIN), measured values (MV) and 3rd polynomial curve (P3). Intra-individual coefficients of variation (CVs) and limits of agreement were calculated. CV for Fatmax determined with SIN was 16.4% and tended to be lower than with P3 and MV (18.6% and 20.8%, respectively). Limits of agreement for Fatmax were -2±27% of [Formula: see text] with SIN, -4±32 with P3 and -4±28 with MV. CVs of oxygen uptake, carbon dioxide production and respiratory exchange rate were <10% at rest and <5% during exercise. Conversely, CVs of fat oxidation rates (20% at rest and 24-49% during exercise) and carbohydrate oxidation rates (33.5% at rest, 8.5-12.9% during exercise) were higher. The intra-individual variability of Fatmax and fat oxidation rates was high (CV>15%), regardless of the data analysis approach employed. Further research on the determinants of the variability of Fatmax and fat oxidation rates is required.

Vibration Training Elicits a Mixed Aerobic and Resistance-type Exercise in Sedentary Subjects

PURPOSE: We hypothesize that untrained subjects can benefit from a greater cardiovascular stimulation than trained athletes, resembling classical aerobic-type activity, in addition to eliciting strength gains.METHODS: 3 groups of male subjects, inactive (SED), endurance trained (END) and strength trained (STR) underwent fitness (VO2max) and lower-body strength tests (isokinetic). Subjects were submitted to a session of oscillating VT, composed of 3 exercises (isometric half-squat, dynamic squat, dynamic squat with added load), each of 3 minutes duration, and repeated at 3 vibration frequencies (20, 26 and 32 Hz). VO2, heart rate and Borg scale were monitored.RESULTS: 27 healthy subjects (10 SED, 9 END and 8 STR), mean age 24.5 (SED), 25.0 (STR) and 29.8 (END) were included. VO2max was significantly different as expected (47.9 vs. 52.9 vs. 63.9 mL?min-1?kg-1, resp. for SED, STR and END). Isokinetic dominant leg extensors strength was higher in STR (3.32 N?m?kg-1 vs. 2.60 and 2.74 in SED and END). During VT, peak oxygen consumption (% of VO2max) attained was 59.3 in SED, 50.8 in STR and 48.0 in END (P<0.001 between SED and other subjects). Peak heart rate (% of heart rate max) was 82.7 in SED, 80.4 in STR and 72.4 in END. In SED, dynamic exercises without extra load elicited 51.0 % of VO2max and 72.1 % of heart rate max, and perceived effort reached 15.1/20.CONCLUSIONS: VT is an unconventional type of exercise, known to enhance strength, bone density, balance and flexibility. Users are attracted by the relative passivity. In SED, VT elicits sufficient cardiovascular response to benefit overall fitness in addition to the strength effects. VT's higher acceptance as an exercise in sedentary people, compared to jogging or cycling, can lead to better adherence to physical activity. Although long-term effects of VT on health are not available, we believe this type of mixed aerobic and resistance-type exercise can be beneficial on multiple health parameters, especially cardiovascular health.

Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers.

Background: Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). Methods: Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. Results: The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. Conclusion: This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

Effect of a small dose of alcohol on the endurance performance of trained cyclists.

AIM: The aim of this study was to investigate the effect of an acute small ethanol (EtOH) dose (0.5 ml EtOH/kg fat-free mass, combined with carbohydrate) in a drink on endurance performance of trained cyclists. METHODS: Thirteen well-trained male cyclists took part in this study. A 60-min cycling endurance performance test (time trial) was performed in a calorimetric chamber after drinking an EtOH (30 +/- 1.8 ml) or a non-EtOH control (C) drink. RESULTS: Overall, EtOH induced a significant decrease in the average cycling power output (PO) (EtOH: 233 +/- 23 W versus C: 243 +/- 24 W, P < 0.01). The time course of mechanical PO showed an early decrease during the EtOH trial as compared to C (P < 0.01). Due to the lower PO, oxygen consumption, carbon dioxide production and glucose oxidation were significantly lower (P < 0.05) as compared to C. Relative to PO, heart rate response and ratings of perceived exertion (RPE) were increased by EtOH as compared to C (P < 0.05). In contrast, EtOH did not influence gross work efficiency, glycaemia and blood lactate concentration. CONCLUSIONS: These results show that the acute low dose of EtOH decreased endurance performance. An increase of cardio-vascular strain and psychobiological mechanisms may explain this decrease of endurance performance.