Influence of timing of milk consumption coupled with endurance training on body composition and endurance training adaptations in humans.

Consumption of low-fat milk (LFM) after resistance training has been shown to have positive influences on body composition and training adaptations; however, little research has examined the effects of LFM consumption following endurance training. The purpose of the study was to look at the effects of combining additional servings of LFM following endurance exercise on body composition, bone health, and training adaptations. 40 healthy males were recruited. Individuals were randomized into 4 groups – DEI (750mL LFM immediately post exercise), DEA (750mL LFM 4 hrs prior to or 6 hrs post exercise), CEI (750mL carbohydrate beverage immediately post-exercise), and CEA (750mL carbohydrate beverage immediately post-exercise). Participants took part in a 12-week endurance training intervention (1 h/day, 3 d/wk, ~60% max HR). 22 participants completed the study. Analysis showed significant increases in lean mass, spinal bone mineral content, relative VO2peak, and a decrease in Trap 5β across all groups (p < 0.05).

Modalities of exercise training on liver fat accretion and inflammatory markers in ovariectomized rats

Les facteurs de risque des maladies cardiovasculaires, telle, que la détérioration du profil lipidique, deviennent plus prononcés après la ménopause, ce qui fait de la maladie coronarienne, l’une des principales causes de décès chez les femmes ménopausées. Une proportion importante de femmes prennent du poids après la ménopause en particulier dans la région abdominale entraînant par conséquent des perturbations métaboliques. Des données récentes suggèrent également que l’absence des œstrogènes observée à la ménopause favorise le développement de la stéatose hépatique. Cette dernière a été incriminée pour incriminée dans le développement de la résistance à l'insuline, et est de ce fait considérée comme une composante hépatique du syndrome métabolique. Il est impératif d'établir des stratégies visant à contrecarrer l'accumulation de graisse dans le foie et l’accroissement du tissu adipeux chez les femmes ménopausées, en tenant compte que l'utilisation de l'hormonothérapie substitutive est de nos jours moins soutenue. Les quatre études de la présente thèse ont été conduites pour tenter de fournir des informations sur le traitement et la prévention de l’augmentation de la masse graisseuse et de la stéatose hépatique qu’entraîne la suppression des œstrogènes, à travers les modifications du mode de vie (diète et exercice physique) chez la rate ovariectomizée (Ovx); un modèle animal de la ménopause. Dans les deux premières études nous nous sommes concentrés sur l’augmentation de la masse graisseuse et sa reprise suite à une perte de poids. Dans la première étude, nous avons montré que les rates Ovx qui ont suivi un programme de restriction alimentaire (FR) ont diminué significativement (P < 0.01) leur poids corporel, leur contenu en graisses intra-abdominales ainsi que leurs triacylglycérols (TAG) hépatiques, comparativement aux rates Ovx nourries à la diète normale. De plus, l’entraînement en résistance (RT) a prévenu la reprise de poids corporel ainsi que l’accroissement du tissu adipeux et l’accumulation de lipides dans le foie des rates Ovx, après l’arrêt du régime amaigrissant. Les résultats de la deuxième étude ont confirmé l'efficacité de la restriction alimentaire associée à l’entraînement en résistance (FR + RT) dans la réduction du poids corporel, des lipides dans le foie et le tissu adipeux chez les rates Ovx. Tenant compte des résultats de notre première étude, l’entraînement en résistance seulement a constitué un atout pour atténuer le poids corporel et la masse grasse reprise par les rates Ovx suite à un programme de perte de poids (FR + RT); bien que l'impact ait été moindre comparé au maintien seul de la restriction alimentaire. De la même manière que la supplémentation en œstrogènes, les résultats de la troisième étude indiquent que l'entraînement en endurance mené concurremment avec l’ovariectomie a significativement atténué l'accumulation de lipides dans le foie ainsi que dans le tissu adipeux. Toutefois, l’entraînement en endurance effectué avant l'ovariectomie n'a pas protégé contre l'accumulation des graisses qu’entraîne l'ovariectomie, si celui-ci est interrompu après l'ovariectomie. Enfin, pour compléter les résultats antérieurs, nous avons montré dans la quatrième étude que l’expression des gènes impliqués dans la synthèse de lipide; SREBP-1c, SCD-1, ChREBP, et ACC dans le foie a augmenté après le retrait des œstrogènes, tandis qu’une diminution (P < 0.01) des niveaux d'ARNm de PPAR-α a été observée. De plus, l'expression hépatique des gènes des cytokines pro-inflammatoires incluant IKKβ, IL-6 ainsi que le contenu protéinique de NF-кB étaient augmentés (P < 0.01) chez les rates Ovx par rapport aux rates ayant subi une Ovx simulée (Sham). Toutes ces perturbations ont été améliorées avec la supplémentation en œstrogènes seulement, ainsi qu'avec l'entraînement en endurance seulement. Dans l'ensemble, nos résultats indiquent que l'exercice physique (en résistance ou en endurance) a un impact significatif sur la réduction de l'accumulation des lipides dans le foie et dans le tissu adipeux des rates Ovx. De plus, chez les rates Ovx, l’entraînement en endurance mimerait les effets des œstrogènes sur l'expression des gènes impliqués dans l'accumulation de lipides et l’inflammation préclinique dans le foie.

EFFECT OF ENDURANCE TRAINING ON HYPOTHALAMIC SEROTONIN CONCENTRATION AND PERFORMANCE

Serotonin is a neurotransmitter that modulates several functions, such as food intake, energy expenditure, motor activity, mood and sleep. Acute exhaustive endurance exercise increases the synthesis, concentration and metabolism of serotonin in the brain. This phenomenon could be responsible for central fatigue after prolonged and exhaustive exercise. However, the effect of chronic exhaustive training on serotonin is not known. The present study was conducted to examine the effect of exhaustive endurance training on performance and serotonin concentrations in the hypothalamus of trained rats. Rats were divided into three groups: sedentary rats (SED), moderately trained rats (MOD) and exhaustively trained rats (EXT), with an increase of 200% in the load carried during the final week of training. Hypothalamic serotonin concentrations were similar between the SED and MOD groups, but were higher in the EXT group (P < 0.05). Performance was lower in the EXT group compared with the MOD group (P < 0.05). Thus, the present study demonstrates that exhaustive training increases serotonin concentrations in the hypothalamus, together with decreased endurance performance after inadequate recovery time. However, the mechanism underlying these changes remains unknown.

Endurance training activates AMP-activated protein kinase, increases expression of uncoupling protein 2 and reduces insulin secretion from rat pancreatic islets

Endurance exercise is known to enhance peripheral insulin sensitivity and reduce insulin secretion. However, it is unknown whether the latter effect is due to the reduction in plasma substrate availability or alterations in beta-cell secretory machinery. Here, we tested the hypothesis that endurance exercise reduces insulin secretion by altering the intracellular energy-sensitive AMP-activated kinase (AMPK) signaling pathway. Male Wistar rats were submitted to endurance protocol training one, three, or five times per week, over 8 weeks. After that, pancreatic islets were isolated, and glucose-induced insulin secretion (GIIS), glucose transporter 2 (GLUT2) protein content, total and phosphorylated calmodulin kinase kinase (CaMKII), and AMPK levels as well as peroxisome proliferator-activated receptor-gamma coactivator-1-alpha (PGC-1 alpha) and uncoupling protein 2 (UCP2) content were measured. After 8 weeks, chronic endurance exercise reduced GIIS in a dose-response manner proportionally to weekly exercise frequency. Contrariwise, increases in GLUT2 protein content, CaMKII and AMPK phosphorylation levels were observed. These alterations were accompanied by an increase in UCP2 content, probably mediated by an enhancement in PGC-1 alpha protein expression. In conclusion, chronic endurance exercise induces adaptations in beta-cells leading to a reduction in GIIS, probably by activating the AMPK signaling pathway. Journal of Endocrinology (2011) 208, 257-264

Exercise training enhances rat pancreatic islets anaplerotic enzymes content despite reduced insulin secretion

Endurance exercise has been shown to reduce pancreatic islets glucose-stimulated insulin secretion (GSIS). Anaplerotic/cataplerotic pathways are directly related to GSIS signaling. However, the effect of endurance training upon pancreatic islets anaplerotic enzymes is still unknown. In this sense, we tested the hypothesis that endurance exercise decreases GSIS by reducing anaplerotic/cataplerotic enzymes content. Male Wistar rats were randomly assigned to one of the four experimental groups as follows: control sedentary group (CTL), trained 1 day per week (TRE1x), trained 3 days per week (TRE3x) and trained 5 days per week (TRE5x) and submitted to an 8 weeks endurance-training protocol. After the training protocol, pancreatic islets were isolated and incubated with basal (2.8 mM) and stimulating (16.7 mM) glucose concentrations for GSIS measurement by radioimmunoassay. In addition, pyruvate carboxylase (PYC), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), ATP-citrate lyase (ACL) and glutamate dehydrogenase (GDH) content were quantified by western blotting. Our data showed that 8 weeks of chronic endurance exercise reduced GSIS by 50% in a dose-response manner according to weekly exercise frequency. PYC showed significant twofold increase in TRE3x. PYC enhancement was even higher in TRE5x (p < 0.0001). PDH and PDK4 reached significant 25 and 50% enhancement, respectively compared with CTL. ACL and GDH also reported significant 50 and 75% increase, respectively. The absence of exercise-induced correlations among GSIS and anaplerotic/cataplerotic enzymes suggests that exercise may control insulin release by activating other signaling pathways. The observed anaplerotic and cataplerotic enzymes enhancement might be related to beta-cell surviving rather than insulin secretion.

Chronic exercise decreases cytokine production in healthy rat skeletal muscle

Skeletal muscle is the source of pro- and anti-inflammatory cytokines, and recently, it has been recognized as an important source of interleukin-6 (IL-6). Acute physical exercise is known to induce a pro-inflammatory cytokine profile in the plasma. However, the effect of chronic physical exercise in the production of pro- and anti-inflammatory cytokines by the skeletal muscle has never been examined. We assessed IL-6, TNF-alpha, IL-1 beta and IL-10 levels in the skeletal muscle of rats submitted to endurance training. Animals were randomly assigned to either a Sedentary group (S, n = 7) or an endurance exercise trained group (T, n = 8). Trained rats ran on a treadmill for 5 days week(-1) for 8 weeks (60% VO(2max)). Detection of IL-6, TNF-alpha, IL-1 beta and IL-10 protein expression was carried out by ELISA. We found decreased expression of IL-1 beta, IL-6, TNF-alpha and IL-10 (28%, 27%. 32% and 37%, respectively, p < 0.05) in the extensor digital longus (EDL) from T, when compared with S. In the soleus, IL-1 beta, TNF-alpha and IL-10 protein levels were similarly decreased (34%, 42% and 50%, respectively, p < 0.05) in T in relation to S, while IL-6 expression was not affected by the training protocol. In conclusion, exercise training induced decreased cytokine protein expression in the skeletal muscle. These data show that in healthy rats, 8-week moderate-intensity aerobic training down regulates skeletal muscle production of cytokines involved in the onset, maintenance and regulation of inflammation, and that the response is heterogeneous according to fibre composition. Copyright (C) 2009 John Wiley & Sons, Ltd.

5-AMINOLEVULINIC ACID-INDUCED ALTERATIONS OF OXIDATIVE-METABOLISM IN SEDENTARY AND EXERCISE-TRAINED RATS

5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria patients and lead-exposed individuals, has previously been shown to autoxidize with generation of reactive oxygen species and to cause in vitro oxidative damage to rat liver mitochondria. We now demonstrate that chronically ALA-treated rats (40 mg/kg body wt every 2 days for 15 days) exhibit decreased mitochondrial enzymatic activities (superoxide dismutase, citrate synthase) in liver and soleus (type I, red) and gastrocnemius (type IIb, white) muscle fibers. Previous adaptation of rats to endurance exercise, indicated by augmented (cytosolic) CuZn-superoxide dismutase (SOD) and (mitochondrial) Mn-SOD activities in several organs, does not protect the animals against liver and soleus mitochondrial damage promoted by intraperitoneal injections of ALA. This is suggested by loss of citrate synthase and Mn-SOD activities and elevation of serum lactate levels, concomitant to decreased glycogen content in soleus and the red portion of gastrocnemius (type IIa) fibers of both sedentary and swimming-trained ALA-treated rats. In parallel, the type IIb gastrocnemius fibers, which are known to obtain energy mainly by glycolysis, do not undergo these biochemical changes. Consistently, ALA-treated rats under swimming training reach fatigue significantly earlier than the control group. These results indicate that ALA may be an important prooxidant in vivo.

Maximal lactate steady state in running mice: Effect of exercise training

1. Maximal lactate steady state (MLSS) corresponds to the highest blood lactate concentration (MLSSc) and workload (MLSSw) that can be maintained over time without continual blood lactate accumulation and is considered an important marker of endurance exercise capacity. The present study was undertaken to determine MLSSw and MLSSc in running mice. In addition, we provide an exercise training protocol for mice based on MLSSw.2. Maximal lactate steady state was determined by blood sampling during multiple sessions of constant-load exercise varying from 9 to 21 m/min in adult male C57BL/6J mice. The constant-load test lasted at least 21 min. The blood lactate concentration was analysed at rest and then at 7 min intervals during exercise.3. The MLSSw was found to be 15.1 +/- 0.7 m/min and corresponded to 60 +/- 2% of maximal speed achieved during the incremental exercise testing. Intra- and interobserver variability of MLSSc showed reproducible findings. Exercise training was performed at MLSSw over a period of 8 weeks for 1 h/day and 5 days/week. Exercise training led to resting bradycardia (21%) and increased running performance (28%). of interest, the MLSSw of trained mice was significantly higher than that in sedentary littermates (19.0 +/- 0.5 vs 14.2 +/- 0.5 m/min; P = 0.05), whereas MLSSc remained unchanged (3.0 mmol/L).4. Altogether, we provide a valid and reliable protocol to improve endurance exercise capacity in mice performed at highest workload with predominant aerobic metabolism based on MLSS assessment.

Maximal lactate steady state in rats submitted to swimming exercise

The higher concentration during exercise at which lactate entry in blood equals its removal is known as 'maximal lactate steady state' (MLSS) and is considered an important indicator of endurance exercise capacity. The aim of the present study was to determine MLSS in rats during swimming exercise. Adult male Wistar rats, which were adapted to water for 3 weeks, were used. After this, the animals were separated at random into groups and submitted once a week to swimming sessions of 20 min, supporting loads of 5, 6, 7, 8, 9 or 10% of body wt. for 6 consecutive weeks. Blood lactate was determined every 5 min to find the MLSS. Sedentary animals presented MLSS with overloads of 5 and 6% at 5.5 mmol/l blood lactate. There was a significant (P < 0.05) increase in blood lactate with the other loads. In another set of experiments, rats of the same strain, sex and age were submitted daily to 60 min of swimming with an 8% body wt. overload, 5 days/week, for 9 weeks. The rats were then submitted to a swimming session of 20 min with an 8% body wt. overload and blood lactate was determined before the beginning of the session and after 10 and 20 min of exercise. Sedentary rats submitted to the same acute exercise protocol were used as a control. Physical training did not alter the MLSS value (P < 0.05) but shifted it to a higher exercise intensity (8% body wt. overload). Taken together these results indicate that MLSS measured in rats in the conditions of the present study was reproducible and seemed to be independent of the physical condition of the animals. © 2001 Elsevier B.V. All rights reserved.

Effect of Cycling Exercise at Different Pedal Cadences on Subsequent Muscle Strength

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exercise training as treatment in cancer cachexia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exercise training improves ambulatory blood pressure but not arterial stiffness in heart transplant recipients

BACKGROUND: Hypertension is the most prevalent comorbidity after heart transplantation (HT). Exercise training (ET) is widely recommended as a key non-pharmacologic intervention for the prevention and management of hypertension, but its effects on ambulatory blood pressure (ABP) and some mechanisms involved in the pathophysiology of hypertension have not been studied in this population. The primary purpose of this study was to investigate the effects of ET on ABP and arterial stiffness of HT recipients.METHODS: 40 HT patients, randomized to ET (n = 31) or a control group (n = 9) underwent a maximal graded exercise test, 24-hour ABP monitoring, and carotid-femoral pulse wave velocity (PWV) assessment before the intervention and at a 12-week follow-up assessment. The ET program was performed thrice-weekly and consisted primarily of endurance exercise (40 minutes) at similar to 70% of maximum oxygen uptake (Vo(2MAX))RESULTS: The ET group had reduced 24-hour (4.0 +/- 1.4 mm Hg, p < 0.01) and daytime (4.8 +/- 1.6 mm Hg, p < 0.01) systolic ABP, and 24-hour (7.0 +/- 1.4 mm Hg, p < 0.001) daytime (7.5 +/- 1.6 mm Hg, p < 0.001) and nighttime (5.9 +/- 1.5 mm Hg, p < 0.001) diastolic ABP after the intervention. The ET group also had improved Vo(2MAX) (9.7% +/- 2.6%, p < 0.001) after the intervention. However, PWV did not change after ET. No variable was changed in the control group after the intervention.CONCLUSIONS: The 12-week ET program was effective for reducing ABP but not PWV in heart transplant recipients. This result suggesfs that endurance ET may be a tool to counteract hypertension in this high-risk population. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.

Exercise-induced angiogenesis correlates with the up-regulated expression of neuronal nitric oxide synthase (nNOS) in human skeletal muscle

The contribution of neuronal nitric oxide synthase (nNOS) to angiogenesis in human skeletal muscle after endurance exercise is controversially discussed. We therefore ascertained whether the expression of nNOS is associated with the capillary density in biopsies of the vastus lateralis (VL) muscle that had been derived from 10 sedentary male subjects before and after moderate training (four 30-min weekly jogging sessions for 6 months, with a heart-rate corresponding to 75% VO(2)max). In these biopsies, nNOS was predominantly expressed as alpha-isoform with exon-mu and to a lesser extent without exon-mu, as determined by RT-PCR. The mRNA levels of nNOS were quantified by real-time PCR and related to the capillary-to-fibre ratio and the numerical density of capillaries specified by light microscopy. If the VL biopsies of all subjects were co-analysed, mRNA levels of nNOS were non-significantly elevated after training (+34%; P > 0.05). However, only five of the ten subjects exhibited significant (P ≤ 0.05) elevations in the capillary-to-fibre ratio (+25%) and the numerical density of capillaries (+21%) and were thus undergoing angiogenesis. If the VL biopsies of these five subjects alone were evaluated, the mRNA levels of nNOS were significantly up-regulated (+128%; P ≤ 0.05) and correlated positively (r = 0.8; P ≤ 0.01) to angiogenesis. Accordingly, nNOS protein expression in VL biopsies quantified by immunoblotting was significantly increased (+82%; P ≤ 0.05) only in those subjects that underwent angiogenesis. In conclusion, the expression of nNOS at mRNA and protein levels was statistically linked to capillarity after exercise suggesting that nNOS is involved in the angiogenic response to training in human skeletal muscle.

Molecular mechanisms of muscle plasticity with exercise

The skeletal muscle phenotype is subject to considerable malleability depending on use. Low-intensity endurance type exercise leads to qualitative changes of muscle tissue characterized mainly by an increase in structures supporting oxygen delivery and consumption. High-load strength-type exercise leads to growth of muscle fibers dominated by an increase in contractile proteins. In low-intensity exercise, stress-induced signaling leads to transcriptional upregulation of a multitude of genes with Ca2+ signaling and the energy status of the muscle cells sensed through AMPK being major input determinants. Several parallel signaling pathways converge on the transcriptional co-activator PGC-1α, perceived as being the coordinator of much of the transcriptional and posttranscriptional processes. High-load training is dominated by a translational upregulation controlled by mTOR mainly influenced by an insulin/growth factor-dependent signaling cascade as well as mechanical and nutritional cues. Exercise-induced muscle growth is further supported by DNA recruitment through activation and incorporation of satellite cells. Crucial nodes of strength and endurance exercise signaling networks are shared making these training modes interdependent. Robustness of exercise-related signaling is the consequence of signaling being multiple parallel with feed-back and feed-forward control over single and multiple signaling levels. We currently have a good descriptive understanding of the molecular mechanisms controlling muscle phenotypic plasticity. We lack understanding of the precise interactions among partners of signaling networks and accordingly models to predict signaling outcome of entire networks. A major current challenge is to verify and apply available knowledge gained in model systems to predict human phenotypic plasticity.

Skeletal muscle (1) H MRSI before and after prolonged exercise. I. muscle specific depletion of intramyocellular lipids

Aim of the study was to determine distribution and depletion patterns of intramyocellular lipids (IMCL) in leg muscles before and after two types of standardized endurance exercise. ¹H-magnetic resonance spectroscopic imaging was performed (1) in the thigh of eight-trained cyclists after exercising on an ergometer for 3 h at 52 ± 8% of maximal speed and (2) in the lower leg of eight-trained runners after exercising on a treadmill for 3 h at 49 ± 3% of maximal workload. Pre-exercise IMCL contents were reduced postexercise in 11 out of 13 investigated upper and lower leg muscles (P < 0.015 for all). A strong linear correlation with a slope of ∼0.5 between pre-exercise IMCL content and IMCL depletion was found. IMCL depletion differed strongly between muscles. Absolute and also relative IMCL reduction was significantly higher in muscles with predominantly slow fibers compared to those with fast fibers. Creatine levels and fiber orientation were stable and unchanged after exercise, while trimethyl-ammonium groups increased. This is presented in the accompanying paper. In conclusion, a systematic comparison of metabolic changes in cross sections of the upper and lower leg was performed. The results imply that pre-exercise IMCL levels determine the degree of IMCL depletion after exercise.