Association between muscle aerobic capacity and whole-body peak oxygen uptake.

PURPOSE: Decline in skeletal muscle mitochondrial oxidative capacity (MOC) is associated with reduced aerobic capacity and increased risk of cardiovascular and metabolic disease. Measuring skeletal muscle MOC may be an alternative method to assess aerobic capacity, especially for individuals unable to perform a whole-body maximum oxygen uptake protocol. In this study, linear regression analysis in two leg muscles was performed to determine whether MOC values could be used to predict whole-body peak oxygen uptake. METHODS: MOC was measured with near infrared spectroscopy (NIRS) in the medial gastrocnemius (MG) and vastus lateralis (VL) muscles of 26 participants (age, 27.1 ± 5.8 years old). Whole-body peak oxygen uptake (VO2 peak) was determined by indirect calorimetry during a continuous ramp protocol on a cycle ergometer. RESULTS: VO2 peak values were significantly correlated with the muscle recovery rate constant (k) of the MG (kMG, r = 0.59; p < 0.01) and VL (kVL, r = 0.63; p < 0.01) muscles. Summing recovery rate constants of both muscles together (kMG + kVL) improved the strength of the correlation with VO2 peak (r = 0.78; p < 0.0001) and could explain a majority of the variance (R2 = 0.61) between the two measurements. CONCLUSION: Data suggest that NIRS can provide reliable MOC measurements on two leg muscles that correlate well with whole-body peak oxygen uptake.

"Teaching somebody else makes you a better person:" A phenomenological exploration of the importance of informal peer support for individuals with spinal cord injury.

BACKGROUND: Peer support is widely recognized as an important aspect of health promotion for individuals with spinal cord injury (SCI). Reports indicate positive effects for the recipients of either informal and formal peer support. The experience can also be meaningful to the person(s) providing support, although the value to providers is not well studied. OBJECTIVE: This study examines the experience of provision of and receipt of informal peer support for individuals with SCI through semi-structured interviews. METHODS: Data were analysed using a qualitative phenomenological approach. 16 participants with SCI participated in the study. RESULTS: Three main themes were developed, each describing different benefits of peer support from the perspective of both members of the peer support dyad. First, participants found personal satisfaction from using their own experiences to help others adjust to their disability. Participants also noted that they learned how to complete activities of daily living as well as how to be autonomous in travel from others with SCI. Finally, participants spoke of the intrinsic benefit in teaching others with SCI. CONCLUSIONS: This study provides a novel understanding of the importance of informal peer support for individuals with SCI. Practitioners should provide opportunities for individuals with SCI to develop informal peer relationships with others who have sustained SCI.

Functional and biochemical characterization of soleus muscle in Down syndrome mice: insight into the muscle dysfunction seen in the human condition.

Persons with Down syndrome (DS) exhibit low muscle strength that significantly impairs their physical functioning. The Ts65Dn mouse model of DS also exhibits muscle weakness in vivo and may be a useful model to examine DS-associated muscle dysfunction. Therefore, the purpose of this experiment was to directly assess skeletal muscle function in the Ts65Dn mouse and to reveal potential mechanisms of DS-associated muscle weakness. Soleus muscles were harvested from anesthetized male Ts65Dn and wild-type (WT) colony controls. In vitro muscle contractile experiments revealed normal force generation of nonfatigued Ts65Dn soleus, but a 12% reduction in force was observed during recovery from fatiguing contractions compared with WT muscle (P < 0.05). Indicators of oxidative stress and mitochondrial oxidative capacity were assessed to reveal potential mechanisms of DS-associated muscle weakness. Protein expression of copper-zinc superoxide dismutase (SOD1), a triplicated gene in persons with DS and Ts65Dn mice, was increased 25% (P < 0.05) in Ts65Dn soleus. Nontriplicated antioxidant protein expression was similar between groups. Lipid peroxidation was unaltered in Ts65Dn animals, but protein oxidation was 20% greater compared with controls (P < 0.05). Cytochrome-c oxidase expression was 22% lower in Ts65Dn muscle (P < 0.05), while expression of citrate synthase was similar between groups. Microarray analysis revealed alteration of numerous pathways in Ts65Dn muscle, including proteolysis, glucose and fat metabolism, neuromuscular transmission, and ATP biosynthesis. In summary, despite biochemical and gene expression differences in soleus muscle of Ts65Dn animals, the functional properties of skeletal muscle likely contribute a minor part to the in vivo muscle weakness.

Exercise-mediated reinnervation of skeletal muscle in elderly people: An update.

Sarcopenia is defined by the loss of muscle mass and function. In aging sarcopenia is due to mild chronic inflammation but also to fiber-intrinsic defects, such as mitochondrial dysfunction. Age-related sarcopenia is associated with physical disability and lowered quality of life. In addition to skeletal muscle, the nervous tissue is also affected in elderly people. With aging, type 2 fast fibers preferentially undergo denervation and are reinnervated by slow-twitch motor neurons. They spread forming new neuro-muscular junctions with the denervated fibers: the result is an increased proportion of slow fibers that group together since they are associated in the same motor unit. Grouping and fiber type shifting are indeed major histological features of aging skeletal muscle. Exercise has been proposed as an intervention for age-related sarcopenia due to its numerous beneficial effects on muscle mechanical and biochemical features. In 2013, a precursor study in humans was published in the European Journal of Translation Myology (formerly known as Basic and Applied Myology), highlighting the occurrence of reinnervation in the musculature of aged, exercise-trained individuals as compared to the matching control. This paper, entitled «Reinnervation of Vastus lateralis is increased significantly in seniors (70-years old) with a lifelong history of high-level exercise¼, is now being reprinted for the second issue of the «Ejtm Seminal Paper Series¼. In this short review we discuss those results in the light of the most recent advances confirming the occurrence of exercise-mediated reinnervation, ultimately preserving muscle structure and function in elderly people who exercise.

"It Helps Me With Everything": A Qualitative Study of the Importance of Exercise for Individuals With Spinal Cord Injury.

Background: The influence of exercise after spinal cord injury (SCI) is a topic important to both clinicians and researchers. The impact of exercise for individuals with SCI is often studied quantitively, with a large focus on the physiological adaptations to exercise intervention. Objectives: This study explores individualized experiences of exercise for people with SCI. Methods: A phenomenological approach was utilized to qualitatively study the experiences of exercise for 16 individuals with SCI. Results: Participants described multiple benefits of exercise, including increased independence, improved mental health, and increased engagement in social activity. Conclusion: This study provides novel information about attitudes toward exercise held by individuals with SCI and a more thorough understanding of concepts that are well researched.

Electromyography-Driven Exergaming in Wheelchairs on a Mobile Platform: Bench and Pilot Testing of the WOW-Mobile Fitness System.

BACKGROUND: Implementing exercises in the form of video games, otherwise known as exergaming, has gained recent attention as a way to combat health issues resulting from sedentary lifestyles. However, these exergaming apps have not been developed for exercises that can be performed in wheelchairs, and they tend to rely on whole-body movements. OBJECTIVE: This study aims to develop a mobile phone app that implements electromyography (EMG)-driven exergaming, to test the feasibility of using this app to enable people in wheelchairs to perform exergames independently and flexibly in their own home, and to assess the perceived usefulness and usability of this mobile health system. METHODS: We developed an Android mobile phone app (Workout on Wheels, WOW-Mobile) that senses upper limb muscle activity (EMG) from wireless body-worn sensors to drive 3 different video games that implement upper limb exercises designed for people in wheelchairs. Cloud server recordings of EMG enabled long-term monitoring and feedback as well as multiplayer gaming. Bench testing of data transmission and power consumption were tested. Pilot testing was conducted on 4 individuals with spinal cord injury. Each had a WOW-Mobile system at home for 8 weeks. We measured the minutes for which the app was used and the exergames were played, and we integrated EMG as a measure of energy expended. We also conducted a perceived usefulness and usability questionnaire. RESULTS: Bench test results revealed that the app meets performance specifications to enable real-time gaming, cloud storage of data, and live cloud server transmission for multiplayer gaming. The EMG sampling rate of 64 samples per second, in combination with zero-loss data communication with the cloud server within a 10-m range, provided seamless control over the app exergames and allowed for offline data analysis. Each participant successfully used the WOW-Mobile system at home for 8 weeks, using the app for an average of 146 (range 89-267) minutes per week with the system, actively exergaming for an average of 53% of that time (39%-59%). Energy expenditure, as measured by integrated EMG, was found to be directly proportional to the time spent on the app (Pearson correlation coefficient, r=0.57-0.86, depending on the game). Of the 4 participants, 2 did not exercise regularly before the study; these 2 participants increased from reportedly exercising close to 0 minutes per week to exergaming 58 and 158 minutes on average using the WOW-Mobile fitness system. The perceived usefulness of WOW-Mobile in motivating participants to exercise averaged 4.5 on a 5-point Likert scale and averaged 5 for the 3 participants with thoracic level injuries. The mean overall ease of use score was 4.25 out of 5. CONCLUSIONS: Mobile app exergames driven by EMG have promising potential for encouraging and facilitating fitness for individuals in wheelchairs who have maintained arm and hand mobility.

Glucocorticoid receptor interacting protein-1 restores glucocorticoid responsiveness in steroid-resistant airway structural cells.

Glucocorticoid (GC) insensitivity represents a profound challenge in managing patients with asthma. The mutual inhibition of transcriptional activity between GC receptor (GR) and other regulators is one of the mechanisms contributing to GC resistance in asthma. We recently reported that interferon regulatory factor (IRF)-1 is a novel transcription factor that promotes GC insensitivity in human airway smooth muscle (ASM) cells by interfering with GR signaling (Tliba et al., Am J Respir Cell Mol Biol 2008;38:463-472). Here, we sought to determine whether the inhibition of GR function by IRF-1 involves its interaction with the transcriptional co-regulator GR-interacting protein 1 (GRIP-1), a known GR transcriptional co-activator. We here found that siRNA-mediated GRIP-1 depletion attenuated IRF-1-dependent transcription of the luciferase reporter construct and the mRNA expression of an IRF-1-dependent gene, CD38. In parallel experiments, GRIP-1 silencing significantly reduced GR-mediated transactivation activities. Co-immunoprecipitation and GST pull-down assays showed that GRIP-1, through its repression domain, physically interacts with IRF-1 identifying GRIP-1 as a bona fide transcriptional co-activator for IRF-1. Interestingly, the previously reported inhibition of GR-mediated transactivation activities by either TNF-alpha and IFN-gamma treatment or IRF-1 overexpression was fully reversed by increasing cellular levels of GRIP-1. Together, these data suggest that the cellular accumulation of IRF-1 may represent a potential molecular mechanism mediating altered cellular response to GC through the depletion of GRIP-1 from the GR transcriptional regulatory complexes.

Expression and activation of the oxytocin receptor in airway smooth muscle cells: Regulation by TNFalpha and IL-13.

BACKGROUND: During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs) function in the presence and absence of IL-13 and TNFalpha, cytokines known to be important in asthma. METHOD: Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS) were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL) samples from healthy subjects and those with asthma. RESULTS: PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL)-13 and tumor necrosis factor (TNFalpha) stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFalpha had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL) fluid derived from healthy subjects as well as from those with asthma. CONCLUSION: Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a potential role for inflammation-induced changes in oxytocin receptor signaling in the regulation of airway hyper-responsiveness in asthma.

The metabolic costs of reciprocal supersets vs. traditional resistance exercise in young recreationally active adults.

An acute bout of traditional resistance training (TRAD) increases energy expenditure (EE) both during exercise and in the postexercise period. Reciprocal supersets (SUPERs) are a method of resistance training that alternates multiple sets of high-intensity agonist-antagonist muscle groups with limited recovery. The purpose of this study was to compare the energy cost of SUPERs and TRAD both during and in the postexercise period. We hypothesized that SUPERs would produce greater exercise EE relative to the duration of exercise time and greater excess postexercise oxygen consumption (EPOC) than TRAD of matched work. Ten recreationally active, young men each participated in 2 exercise protocols: SUPER, followed 1 week later by TRAD matched within using a 10-repetition maximum load for 6 exercises, 4 sets, and repetitions. Participants were measured for oxygen consumption and blood lactate concentration during exercise and 60 minutes postexercise after each exercise bout. No significant differences were observed in aerobic exercise EE between trials (SUPER 1,009.99 +/- 71.42 kJ; TRAD 954.49 +/- 83.31 kJ); however, when expressed relative to time, the exercise EE was significantly greater during SUPER (34.70 +/- 2.97 kJ.min) than TRAD (26.28 +/- 2.43 kJ.min). Excess postexercise oxygen consumption was significantly greater after SUPER (79.36 +/- 7.49 kJ) over TRAD (59.67 +/- 8.37 kJ). Average blood lactate measures were significantly greater during SUPER (5.1 +/- 0.9 mmol.L) than during TRAD (3.8 +/- 0.6 mmol.L). Reciprocal supersets produced greater exercise kJ.min, blood lactate, and EPOC than did TRAD. Incorporating this method of resistance exercise may benefit exercisers attempting to increase EE and have a fixed exercise volume with limited exercise time available.

Cloud-based Multiplayer Exergaming: Developing a platform for social interaction as a motivational tool for exercising in the wheelchair community.

In the recent decade, mobile exergaming has emerged as a way to motivate physical activity and thereby increase fitness. It has been found that those which encourage social interaction and multiplayer gaming leads to better fitness outcomes than single player games [1]. However, none have yet to tailor exergames for people who use wheelchairs due to lower mobility impairment. We present a mobile exergaming and fitness tracking app in which the exergames are tailored toward people in wheelchairs and features a virtual community which allows social interaction through multiplayer gaming and leaderboard features. We hypothesized that users would find the multiplayer games more useful for improving fitness than the single player games. However, perceived usefulness survey results indicate overall satisfaction with the main design features but not a particular preference for the multiplayer gaming over single player gaming. Users overall found the app useful and easy to use, and the results provide indication that the virtual community created through the multiplayer feature of the mobile exergaming app does promote and enhance exercising.Clinical relevance- Multiplayer gaming was designed into a mobile fitness app to encourage exercise amongst individuals in wheelchairs. The virtual community created is expected to increase activity levels and its many associated health benefits in this community, promote a greater sense of belonging, and increase social participation.

Cytokines induce an early steroid resistance in airway smooth muscle cells: novel role of interferon regulatory factor-1.

We have previously shown that long-term treatment of airway smooth muscle (ASM) cells with a combination of TNF-alpha and IFN-gamma impaired steroid anti-inflammatory action through the up-regulation of glucocorticoid receptor beta isoform (GRbeta) (Mol Pharmacol 2006;69:588-596). We here found that steroid actions could also be suppressed by short-term exposure of ASM cells to TNF-alpha and IFN-gamma (6 h) as shown by the abrogated glucocorticoid responsive element (GRE)-dependent gene transcription; surprisingly, neither GRalpha nuclear translocation nor GRbeta expression was affected by cytokine mixture. The earlier induction of CD38, a molecule recently involved in asthma, seen with TNF-alpha and IFN-gamma combination but not with cytokine alone, was also completely insensitive to steroid pretreatment. Chromatin-immunoprecipitation (IP) and siRNA strategies revealed not only increased binding of interferon regulatory factor 1 (IRF-1) transcription factor to CD38 promoter, but also its implication in regulating CD38 gene transcription. Interestingly, the capacity of fluticasone to completely inhibit TNF-alpha-induced IRF-1 expression, IRF-1 DNA binding, and transactivation activities was completely lost in cells exposed to TNF-alpha and IFN-gamma in combination. This early steroid dysfunction seen with cytokine combination could be reproduced by enhancing IRF-1 cellular levels using constitutively active IRF-1, which dose-dependently inhibited GRE-dependent gene transcription. Consistently, reducing IRF-1 cellular levels using siRNA approach significantly restored steroid transactivation activities. Collectively, our findings demonstrate for the first time that IRF-1 is a novel alternative GRbeta-independent mechanism mediating steroid dysfunction induced by pro-asthmatic cytokines, in part via the suppression of GRalpha activities.

Essential role of IFNbeta and CD38 in TNFalpha-induced airway smooth muscle hyper-responsiveness.

We recently identified autocrine interferon (IFN)beta as a novel mechanism mediating tumor necrosis factor (TNF)alpha-induced expression of inflammatory genes in airway smooth muscle (ASM) cells, including CD38, known to regulate calcium signaling. Here, we investigated the putative involvement of IFNbeta in regulating TNFalpha-induced airway hyper-responsiveness (AHR), a defining feature of asthma. Using our pharmacodynamic model to assess ex vivo AHR isolated murine tracheal rings, we found that TNFalpha-induced enhanced contractile responses to carbachol and bradykinin was abrogated by neutralizing anti-IFNbeta antibody or in tracheal rings deficient in CD38. In cultured human ASM cells, where CD38 has been involved in TNFalpha-induced enhanced calcium signals to carbachol and bradykinin, we found that neutralizing anti-IFNbeta prevented TNFalpha enhancing action only on carbachol responses but not to that induced by bradykinin. In a well-characterized model of allergic asthma (mice sensitized and challenged with Aspergillus fumigatus (Af)), we found heightened expression of both IFNbeta and CD38 in the airways. Furthermore, allergen-associated AHR to methacholine, assessed by lung resistance and dynamic compliance, was completely suppressed in CD38-deficient mice, despite the preservation of airway inflammation. These data provide the first evidence that ASM-derived IFNbeta and CD38 may play a significant role in the development of TNFalpha-associated AHR.

Role of respiratory system impedance in the difference of ventilatory control between children and adults.

How children are able to adapt their ventilation to the intensity of exercise faster than adults remain unclear. We hypothesized that differences of VE observed between children and adults depend on either peripheral chemoreceptors or central command activity. We examined ventilatory control parameters in either normoxic or hypoxic condition (FI 02 =0.15). We analyzed the adaptability of the respiratory exchanges by (i) the measurement of ventilatory kinetics time-constant and (ii) the central command by the mouth-occlusion pressure (P0.1). A group of nine pre-pubescent children (mean age 9.5+/-1 years) and a group of eight adults (mean age 24+/-3.1 years) performed a constant-load exercise. In normoxia, children had significantly shorter time-constant (tau) VCO2 (respectively, 38.5+/-4.3 and 53.1+/-5.3s; P<0.001), tau VE (respectively, 52.5+/-13.1s vs. 66.1+/-12.3s; P<0.001), and tau P0.1 (57.4+/-15.4 and 61.0+/-12.9s, respectively; P<0.001) than adults. In hypoxia, children exhibited shorter tau P0.1/VT/Ti compare to adults. Reinforced by the significant correlation between tau VE and tau P0.1/VT/Ti for children but not adults, we concluded that ventilatory response differences could be due in part to the respiratory system impedance.

Oxidant production and SOD1 protein expression in single skeletal myofibers from Down syndrome mice.

Down syndrome (DS) is a genetic condition caused by the triplication of chromosome 21. Persons with DS exhibit pronounced muscle weakness, which also occurs in the Ts65Dn mouse model of DS. Oxidative stress is thought to be an underlying factor in the development of DS-related pathologies including muscle dysfunction. High-levels of oxidative stress have been attributed to triplication and elevated expression of superoxide dismutase 1 (SOD1); a gene located on chromosome 21. The elevated expression of SOD1 is postulated to increase production of hydrogen peroxide and cause oxidative injury and cell death. However, it is unknown whether SOD1 protein expression is associated with greater oxidant production in skeletal muscle from Ts65Dn mice. Thus, our objective was to assess levels of SOD1 expression and oxidant production in skeletal myofibers from the flexor digitorum brevis obtained from Ts65Dn and control mice. Measurements of oxidant production were obtained from myofibers loaded with 2',7'-dichlorodihydrofluorescein diacetate (DCFH2-DA) in the basal state and following 15min of stimulated unloaded contraction. Ts65Dn myofibers exhibited a significant decrease in basal DCF emissions (p < 0.05) that was associated with an approximate 3-fold increase in SOD1 (p < 0.05). DCF emissions were not affected by stimulating contraction of Ts65Dn or wild-type myofibers (p > 0.05). Myofibers from Ts65Dn mice tended to be smaller and myonuclear domain was lower (p < 0.05). In summary, myofibers from Ts65Dn mice exhibited decreased basal DCF emissions that were coupled with elevated protein expression of SOD1. Stimulated contraction in isolated myofibers did not affect DCF emissions in either group. These findings suggest the skeletal muscle dysfunction in the adult Ts65Dn mouse is not associated with skeletal muscle oxidative stress.

Effect of an acute bout of aerobic exercise on chemerin levels in obese adults.

AIMS: Serum chemerin concentrations are elevated in obese individuals and may play a role in type 2 diabetes. Exercise improves insulin sensitivity, which may be related to changes in chemerin. This study explored how an acute bout of aerobic exercise affected chemerin levels in non-diabetic obese adults. METHODS: Blood samples from 11 obese adults were obtained during two separate conditions: sedentary (SED) and exercise (EX; 60-65% VO2peak). Samples were drawn at baseline, immediately following exercise and hourly for an additional 2h. ANOVA was used to test for differences in chemerin between conditions. RESULTS: Unadjusted analysis showed no difference in overall change (baseline to 2h post) in chemerin between conditions. During the 2-h post-exercise period, chemerin decreased to 12% below baseline, compared to a 2.5% increase above baseline during that time period on the sedentary day (p=0.06, difference in post-to-2h change between conditions). Controlling for homeostatic model assessment of insulin resistance (HOMA-IR), a significant difference existed between EX and SED in the change in chemerin from baseline to 2-h post (p=0.02). Stratified analyses showed a consistent exercise-induced decrease in chemerin among non-insulin resistant subjects, while chemerin increased during exercise among insulin resistant subjects, and then decreased post-exercise. CONCLUSION: An acute bout of exercise in obese individuals may elicit a drop in chemerin levels during the post-exercise period, and this response may vary based on insulin resistance.

Multiple short bouts of exercise over 12-h period reduce glucose excursions more than an energy-matched single bout of exercise.

OBJECTIVE: Long, uninterrupted bouts of sedentary behavior are thought to negatively influence postprandial glucose and insulin concentrations. We examined the effects of a 1-h bout of morning exercise versus intermittent walking bouts of short duration on glucose excursions and insulin secretion over 12-h. MATERIALS/METHODS: Eleven young, obese individuals (18-35 years, BMI>30kg/m(2)) with impaired glucose tolerance were studied on three 12-h study days: 1) sedentary behavior (SED); 2) sedentary behavior with 1-h morning exercise (EX) at 60%-65% VO2peak; and 3) sedentary behavior with 12-hourly, 5-min intervals of exercise (INT) at 60%-65% VO2peak. Meals (1046kJ/meal) were provided every 2-h. Blood samples were collected every 10 min and measured for glucose, insulin, and c-peptide concentrations. RESULTS: Glucose iAUC (12-h) was attenuated in the INT and SED conditions compared to the EX condition (P<0.05). Glucose concentrations were higher in the EX compared to the SED condition for ~150min (20% of the study day), and comparison of the EX-INT study days revealed that glucose concentrations were greater for~240min (~1/3 of the 12-hday). In the SED condition, the 12-h insulin iAUC was ~15% higher (P<0.05) compared to the INT and EX conditions. Insulin production rate was found to increase ~20% with INT exercise vs. the SED and EX condition (P<0.05). CONCLUSIONS: Short, frequent periods of exercise attenuated glucose excursions and insulin concentrations in obese individuals to a greater degree than an equal amount of exercise performed continuously in the morning.

Physical activity offsets the negative effects of a high-fructose diet.

OBJECTIVE: This study aimed to determine the interaction between a high-fructose diet and PA levels on postprandial lipidemia and inflammation in normal-weight, recreationally active individuals. METHODS: Twenty-two men and women (age, 21.2 ± 0.6 yr; body mass index, 22.5 ± 0.6 kg · m(-2)) consumed an additional 75 g of fructose for 14 d on two separate occasions: high physical activity (PA) (approximately 12,500 steps per day) (FR+active) and low PA (approximately 4500 steps per day) (FR+inactive). A fructose-rich test meal was given before and at the end of each intervention. Blood was sampled at baseline and for 6 h after the meal for triglycerides (TG), VLDL, total cholesterol, glucose, insulin, tumor necrosis factor-α, interleukin 6, and C-reactive protein. RESULTS: Log-transformed TG area under the curve (AUC) significantly increased from before (10.1 ± 0.1 mg · dL(-1) × min for 6 h) to after (10.3 ± 0.08 mg · dL(-1) × min for 6 h, P = 0.04) the FR+inactive intervention, with an 88% increase in Δ peak TG (P = 0.009) and an 84% increase in Δ peak VLDL (P = 0.002). Δ Peak interleukin 6 also increased by 116% after the FR+inactive intervention (P = 0.009). Insulin total AUC significantly decreased after FR+active intervention (P = 0.04), with no change in AUC after the FR+inactive intervention. No changes were observed in glucose, tumor necrosis factor-α, and C-reactive protein concentrations (P > 0.05). CONCLUSIONS: Low PA during a period of high fructose intake augments fructose-induced postprandial lipidemia and inflammation, whereas high PA minimizes these fructose-induced metabolic disturbances. Even within a young healthy population, maintenance of high PA (>12,500 steps per day) decreases susceptibility to cardiovascular risk factors associated with elevated fructose consumption.

Gastric bypass up-regulates insulin signaling pathway.

OBJECTIVE: In the severely obese, Roux-en-Y gastric bypass (RYGB) reverses diabetes before body weight loss occurs. We determined changes in protein expression of insulin receptor (IR), its substrates (IRS1 and IRS2), and their phosphorylated state (p-IR and p-IRS1/2) in skeletal muscle (SM), liver and adipose tissue (AT), and GLUT4 in SM and AT, 14 and 28 d after RYGB to gaining insight into the time-related dynamics of insulin transduction pathway that may contribute to diabetes resolution. BACKGROUND: RYGB induces a rapid weight loss followed by a slower weight loss period, leading to reversal of diabetes. We hypothesize that diabetes reversal is due to RYGB-induced up-regulation of insulin signaling pathway. METHODS: Diet-induced obese rats had RYGB or sham-operation (obese-controls). Daily food intake, body weight, glucose, insulin, and adiponectin were measured. IR, IRS1, IRS2, p-IR, and p-IRS1/2 were measured in SM, liver, and AT and GLUT4 in SM and AT, 14 and 28 d after RYGB, respectively, reflecting the rapid and slower weight loss periods after RYGB. RESULTS: On day 14, in RYGB rats versus obese-controls, food intake, body weight, and fat mass decreased. Rats became normo-glycemic and had low insulin levels and elevated glucose:insulin ratio and decreased adiponectin concentrations. This persisted to day 28, except that adiponectin rose. No change in IR occurred on day 14, in RYGB rats versus obese-controls. By day 28 RYGB rats had a higher IR expression in SM and liver, but no changes in AT. RYGB induced a time-related increase in p-IR in liver and in pIRS1/2 in SM and liver. An increase in GLUT4 occurred by day 28 in SM and AT. CONCLUSIONS: Improvement in diabetes occurred after RYGB due to up-regulation in key insulin pathway proteins at several levels, predominantly in SM and liver in association with ongoing caloric restriction, body weight, and fat mass loss.

STZ-induced skeletal muscle atrophy is associated with increased p65 content and downregulation of insulin pathway without NF-κB canonical cascade activation.

Type 1 diabetes mellitus (DM)-induced skeletal muscle atrophy is associated with an increased incidence in morbidity and mortality. Although the precise mechanism of diabetes-induced skeletal muscle atrophy remains to be established, several NF-κB-dependent pro-inflammatory genes have been identified as potential therapeutic targets. Moreover, activation of NF-κB has previously been shown to be required for cytokine-induced loss of skeletal muscle proteins. Therefore, we investigated activation of the NF-κB canonical pathway, concomitant to insulin signaling activation in skeletal muscle from diabetes-induced rats. Ten rats injected with streptozotocin (STZ) 4 weeks prior to tissue extraction were compared to 10 control rats. Using total, cytosolic and nuclear protein extracts from hindlimb muscles: soleus (SOL), extensor digitorum longus (EDL), gastrocnemius (GM) and liver tissue, we assessed key proteins important for the activation of both NF-κB and insulin pathways. Insulin blood concentration decreased to 3.9 ± 1.2 mU/ml following STZ-injection resulting in hyperglycemia (17.9 ± 0.7 mmol/l). SOL, EDL and GM mass decreased, and liver mass increased following STZ injection. NF-κB/p65 content in SOL, GM and liver increased in STZ-injected rats, without any change in IκB degradation or IKK phosphorylation. Muscle NF-κB/p65 remained bound to IκB and did not translocate or bind to DNA. Although the canonical NF-κB cascade was not activated, STZ induced a decrease in insulin pathway proteins including insulin receptor (IR) and substrate (IRS-1) content and phosphorylation compared to control animals. A downregulation of insulin pathway proteins and muscle atrophy occurred in response to STZ administration, and despite increased p65 content, STZ treatment did not activate the canonical NF-κB cascade. Therefore, it is unlikely that hyperglycemia initiates skeletal muscle atrophy via activation of the NF-κB canonical pathway.