Effect of Galactose Ingestion Before and During Exercise on Substrate Oxidation, Postexercise Satiety, and Subsequent Energy Intake in Females.

OBJECTIVE: To examine the effects of consuming a galactose carbohydrate (CHO) drink on substrate oxidation, postexercise satiety, and subsequent energy intake. METHODS: Nine recreationally active eumenorrheic females undertook 3 trials, each consisting of running for 60 minutes at 65% VO2peak followed immediately by a 90-minute rest period. Prior to (300 ml) and at 15-minute intervals during exercise (150 ml), participants consumed either a glucose (GLU: GI 89) or galactose (GAL: GI 20) drink, each of which contained 45 g of CHO, or an artificially sweetened placebo (PLA). Following the rest period, participants were provided with an ad libitum test lunch and asked to record food intake for the remainder of the day. RESULTS: Plasma glucose was significantly greater throughout exercise and rest following the GLU trial compared with the GAL and PLA trials (P < 0.05); however there were no differences in CHO oxidation. Hunger was significantly lower (P < 0.05) throughout the GAL compared to the GLU and PLA trials. There were no significant differences between trials for energy intake during the postexercise meal. Overall net energy balance for the 24 hours was negative in both the GAL (-162 ± 115 kcal; P < 0.05 vs GLU) and PLA trials (-49 ± 160 kcal). CONCLUSIONS: Results demonstrate that ingesting a solution containing GAL before and during exercise can positively impact postexercise satiety and energy balance throughout the day, compared to a more readily available and widely consumed form of CHO. Despite this, there appears to be no apparent benefit in consuming a CHO beverage on fuel utilization for this moderate exercise intensity and duration

Cooling interventions for athletes: An overview of effectiveness, physiological mechanisms, and practical considerations.

Exercise-induced increases in core body temperature could negative impact performance and may lead to development of heat-related illnesses. The use of cooling techniques prior (pre-cooling), during (per-cooling) or directly after (post-cooling) exercise may limit the increase in core body temperature and therefore improve exercise performance. The aim of the present review is to provide a comprehensive overview of current scientific knowledge in the field of pre-cooling, per-cooling and post-cooling. Based on existing studies, we will discuss 1) the effectiveness of cooling interventions, 2) the underlying physiological mechanisms and 3) practical considerations regarding the use of different cooling techniques. Furthermore, we tried to identify the optimal cooling technique and compared whether cooling-induced performance benefits are different between cool, moderate and hot ambient conditions. This article provides researchers, physicians, athletes and coaches with important information regarding the implementation of cooling techniques to maintain exercise performance and to successfully compete in thermally stressful conditions

Pre-cooling for endurance exercise performance in the heat: a systematic review.

PMCID: PMC3568721The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1741-7015/10/166. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Endurance exercise capacity diminishes under hot environmental conditions. Time to exhaustion can be increased by lowering body temperature prior to exercise (pre-cooling). This systematic literature review synthesizes the current findings of the effects of pre-cooling on endurance exercise performance, providing guidance for clinical practice and further research

Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle

The development of skeletal muscle insulin resistance is an early physiological defect, yet the intracellular mechanisms accounting for this metabolic defect remained unresolved. Here, we have examined the role of glucose-6-phosphate dehydrogenase (G6PDH) activity in the pathogenesis of insulin resistance in skeletal muscle. Methods Multiple mouse disease states exhibiting insulin resistance and glucose intolerance, as well as obese humans defined as insulin-sensitive, insulin-resistant, or pre-diabetic, were examined. Results We identified increased glucose-6-phosphate dehydrogenase (G6PDH) activity as a common intracellular adaptation that occurs in parallel with the induction of insulin resistance in skeletal muscle and is present across animal and human disease states with an underlying pathology of insulin resistance and glucose intolerance. We observed an inverse association between G6PDH activity and nitric oxide synthase (NOS) activity and show that increasing NOS activity via the skeletal muscle specific neuronal (n)NOS&mu; partially suppresses G6PDH activity in skeletal muscle cells. Furthermore, attenuation of G6PDH activity in skeletal muscle cells via (a) increased nNOS&mu;/NOS activity, (b) pharmacological G6PDH inhibition, or (c) genetic G6PDH inhibition increases insulin-independent glucose uptake. Conclusions We have identified a novel, previously unrecognized role for G6PDH in the regulation of skeletal muscle glucose metabolism. <br /

Metabolic control and sex: A focus on inflammatory-linked mediators

Men and women have many differing biological and physiological characteristics. Thus, it is no surprise that the control of metabolic processes and the mechanisms underlying metabolic-related diseases have sex-specific components. There is a clear metabolic sexual dimorphism in that up until midlife, men have a far greater likelihood of acquiring cardio-metabolic disease than women. Following menopause, however, this difference is reduced, suggestive of a protective role of the female sex hormones. Inflammatory processes have been implicated in the pathogenesis of cardio-metabolic disease with human studies correlating metabolic disease acquisition or risk with levels of various inflammatory markers. Rodent studies employing genetic modifications or novel pharmacological approaches have provided mechanistic insight into the role of these inflammatory mediators. Sex differences impact inflammatory processes and the subsequent biological response. As a consequence, this may affect how inflammation alters metabolic processes between the sexes. Recently, some of our work in the field of inflammatory genes and metabolic control identified a sexual dimorphism in a preclinical model and caused us to question the frequency and scale of such findings in the literature. This review concentrates on inflammatory-related signalling in relation to obesity, insulin resistance, and type 2 diabetes and highlights the differences observed between males and females. Differences in the activation and signalling of various inflammatory genes and proteins present another reason why studying both male and female patients or animals is important in the context of understanding and finding therapeutics for metabolic-related disease

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

Creatine ingestion augments dietary carbohydrate mediated muscle glycogen supercomposition during the initial 24 hrs of recovery following prolonged exhaustive exercise in humans

Muscle glycogen availability can limit endurance exercise performance. We previously demonstrated 5 days of creatine (Cr) and carbohydrate (CHO) ingestion augmented post-exercise muscle glycogen storage compared to CHO feeding alone in healthy volunteers. Here we aimed to characterise the time-course of this Cr-induced response under more stringent and controlled experimental conditions and identify potential mechanisms underpinning this phenomenon. Fourteen healthy, male volunteers cycled to exhaustion at 70% VO2peak. Muscle biopsies were obtained at rest immediately post-exercise and after 1, 3 and 6 days of recovery, during which Cr or placebo supplements (20g.day-1) were ingested along with a prescribed high CHO diet (37.5 kcal.kg body mass-1.day-1, >80% calories CHO). Oral-glucose tolerance tests (oral-GTT) were performed pre-exercise and after 1, 3 and 6 days of Cr and placebo supplementation. Exercise depleted muscle glycogen content to the same extent in both treatment groups. Creatine supplementation increased muscle total-Cr, free-Cr and phosphocreatine (PCr) content above placebo following 1, 3 and 6 days of supplementation (all P<0.05). Creatine supplementation also increased muscle glycogen content noticeably above placebo after 1 day of supplementation (P<0.05), which was sustained thereafter. This study confirmed dietary Cr augments post-exercise muscle glycogen super-compensation, and demonstrates this occurred during the initial 24 h of post-exercise recovery (when muscle total-Cr had increased by <10%). This marked response ensued without apparent treatment differences in muscle insulin sensitivity (oral-GTT, muscle GLUT4 mRNA), osmotic stress (muscle c-fos and HSP72 mRNA) or muscle cell volume (muscle water content) responses, such that another mechanism must be causative

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease

MCL-1 is essential for survival but dispensable for metabolic fitness of FOXP3+ regulatory T cells

FOXP3+ regulatory T (Treg) cells are essential for maintaining immunological tolerance. Given their importance in immune-related diseases, cancer and obesity, there is increasing interest in targeting the Treg cell compartment therapeutically. New pharmacological inhibitors that specifically target the prosurvival protein MCL-1 may provide this opportunity, as Treg cells are particularly reliant upon this protein. However, there are two distinct isoforms of MCL-1; one located at the outer mitochondrial membrane (OMM) that is required to antagonize apoptosis, and another at the inner mitochondrial membrane (IMM) that is reported to maintain IMM structure and metabolism via ATP production during oxidative phosphorylation. We set out to elucidate the relative importance of these distinct biological functions of MCL-1 in Treg cells to assess whether MCL-1 inhibition might impact upon the metabolism of cells able to resist apoptosis. Conditional deletion of Mcl1 in FOXP3+ Treg cells resulted in a lethal multiorgan autoimmunity due to the depletion of the Treg cell compartment. This striking phenotype was completely rescued by concomitant deletion of the apoptotic effector proteins BAK and BAX, indicating that apoptosis plays a pivotal role in the homeostasis of Treg cells. Notably, MCL-1-deficient Treg cells rescued from apoptosis displayed normal metabolic capacity. Moreover, pharmacological inhibition of MCL-1 in Treg cells resistant to apoptosis did not perturb their metabolic function. We conclude that Treg cells require MCL-1 only to antagonize apoptosis and not for metabolism. Therefore, MCL-1 inhibition could be used to manipulate Treg cell survival for clinical benefit without affecting the metabolic fitness of cells resisting apoptosis

Over-expressing the soluble gp130-Fc does not ameliorate methionine and choline deficient diet-induced non alcoholic steatohepatitis in mice

Non-alcoholic steatohepatitis (NASH) is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6) has been implicated in the pathogenesis of NASH, with the so-called IL-6 ‘trans-signaling’ cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 ‘trans-signaling’, using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice) fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet) and hypothesized that markers of NASH would be ameliorated in such mice. Sgp130Fc Tg and littermate control mice were fed a MCD or control diet for 4 weeks. The MCD diet induced many hallmarks of NASH including hepatomegaly, steatosis, and liver inflammation. However, in contrast with other mouse models and, indeed, human NASH, the MCD diet model did not increase the mRNA or protein expression of IL-6. Not surprisingly, therefore, markers of MCD diet-induced NASH were unaffected by sgp130Fc transgenic expression. While the MCD diet model induces many pathophysiological markers of NASH, it does not induce increased IL-6 expression in the liver, a key hallmark of human NASH. We, therefore, caution the use of the MCD diet as a viable mouse model of NASH