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Sample records for alter muscle carbohydrate

  1. Caffeine ingestion does not alter carbohydrate or fat metabolism in human skeletal muscle during exercise

    PubMed Central

    Graham, Terry E; Helge, Jorn W; MacLean, David A; Kiens, Bente; Richter, Erik A

    2000-01-01

    This study examined the effect of ingesting caffeine (6 mg kg−1) on muscle carbohydrate and fat metabolism during steady-state exercise in humans. Young male subjects (n = 10) performed 1 h of exercise (70 % maximal oxygen consumption (V̇O2,max)) on two occasions (after ingestion of placebo and caffeine) and leg metabolism was quantified by the combination of direct Fick measures and muscle biopsies. Following caffeine ingestion serum fatty acid and glycerol concentration increased (P ≤ 0.05) at rest, suggesting enhanced adipose tissue lipolysis. In addition circulating adrenaline concentration was increased (P ≤ 0.05) at rest following caffeine ingestion and this, as well as leg noradrenaline spillover, was elevated (P ≤ 0.05) above placebo values during exercise. Caffeine resulted in a modest increase (P ≤ 0.05) in leg vascular resistance, but no difference was found in leg blood flow. Arterial lactate and glucose concentrations were increased (P ≤ 0.05) by caffeine, while the rise in plasma potassium was dampened (P ≤ 0.05). There were no differences in respiratory exchange ratio or in leg glucose uptake, net muscle glycogenolysis, leg lactate release or muscle lactate, or glucose 6-phosphate concentration. Similarly there were no differences between treatments in leg fatty acid uptake, glycerol release or muscle acetyl CoA concentration. These findings indicate that caffeine ingestion stimulated the sympathetic nervous system but did not alter the carbohydrate or fat metabolism in the monitored leg. Other tissues must have been involved in the changes in circulating potassium, fatty acids, glucose and lactate. PMID:11118510

  2. Chronic oral ingestion of l-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans

    PubMed Central

    Wall, Benjamin T; Stephens, Francis B; Constantin-Teodosiu, Dumitru; Marimuthu, Kanagaraj; Macdonald, Ian A; Greenhaff, Paul L

    2011-01-01

    We have previously shown that insulin increases muscle total carnitine (TC) content during acute i.v. l-carnitine infusion. Here we determined the effects of chronic l-carnitine and carbohydrate (CHO; to elevate serum insulin) ingestion on muscle TC content and exercise metabolism and performance in humans. On three visits, each separated by 12 weeks, 14 healthy male volunteers (age 25.9 ± 2.1 years, BMI 23.0 ± 0.8 kg m−2) performed an exercise test comprising 30 min cycling at 50%, 30 min at 80%, then a 30 min work output performance trial. Muscle biopsies were obtained at rest and after exercise at 50% and 80% on each occasion. Following visit one, volunteers ingested either 80 g of CHO (Control) or 2 g of l-carnitine-l-tartrate and 80 g of CHO (Carnitine) twice daily for 24 weeks in a randomised, double blind manner. All significant effects reported occurred after 24 weeks. Muscle TC increased from basal by 21% in Carnitine (P < 0.05), and was unchanged in Control. At 50%, the Carnitine group utilised 55% less muscle glycogen compared to Control (P < 0.05) and 31% less pyruvate dehydrogenase complex (PDC) activation compared to before supplementation (P < 0.05). Conversely, at 80%, muscle PDC activation was 38% higher (P < 0.05), acetylcarnitine content showed a trend to be 16% greater (P < 0.10), muscle lactate content was 44% lower (P < 0.05) and the muscle PCr/ATP ratio was better maintained (P < 0.05) in Carnitine compared to Control. The Carnitine group increased work output 11% from baseline in the performance trial, while Control showed no change. This is the first demonstration that human muscle TC can be increased by dietary means and results in muscle glycogen sparing during low intensity exercise (consistent with an increase in lipid utilisation) and a better matching of glycolytic, PDC and mitochondrial flux during high intensity exercise, thereby reducing muscle anaerobic ATP production. Furthermore, these changes were associated with an

  3. Carbohydrate feeding during recovery alters the skeletal muscle metabolic response to repeated sessions of high-intensity interval exercise in humans.

    PubMed

    Cochran, Andrew J R; Little, Jonathan P; Tarnopolsky, Mark A; Gibala, Martin J

    2010-03-01

    Exercise training under conditions of reduced carbohydrate (CHO) availability has been reported to augment gains in skeletal muscle oxidative capacity; however, the underlying mechanisms are unclear. We examined the effect of manipulating CHO intake on the acute metabolic response to high-intensity interval exercise, including signaling cascades linked to mitochondrial biogenesis. Ten men performed two trials in random order separated by >or=1 wk. Each trial consisted of a morning (AM) and afternoon (PM) training session (5 x 4 min cycling at approximately 90-95% of heart rate reserve) separated by 3 h of recovery during which subjects ingested a high-CHO drink (HI-HI) or nonenergetic placebo (HI-LO) before PM exercise. Biopsies (vastus lateralis) revealed that muscle phosphocreatine and ATP content were similar after AM exercise but decreased to a greater extent during PM exercise in HI-LO vs. HI-HI. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) and AMP-activated protein kinase (AMPK) increased approximately 4-fold and 2-fold, respectively, during AM exercise with no difference between conditions. After PM exercise, p38 MAPK phosphorylation was higher in HI-LO vs. HI-HI, whereas AMPK was not different between conditions. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha) gene expression increased approximately 8-fold during recovery from AM exercise and remained elevated during PM exercise with no differences between conditions. Cytochrome oxidase subunit 4 (COXIV) mRNA was also elevated 3 h after AM exercise, with no difference between conditions. These data provide evidence that p38 MAPK is a nutrient-sensitive signaling molecule that could be involved in the altered skeletal muscle adaptive response reported after exercise training under conditions of restricted CHO intake, but further research is required to confirm this hypothesis.

  4. Carbohydrate oxidation disorders of skeletal muscle.

    PubMed

    Vorgerd, Matthias; Zange, Jochen

    2002-11-01

    The major energy sources for muscle contraction are glycogen, glucose and fatty acids, and defects in their oxidative pathways cause metabolic myopathies. Eleven specific enzyme deficiencies of carbohydrate oxidation affect skeletal muscle alone or in combination with other tissues, such as liver, heart or red blood cells. These hereditary glycogen storage diseases cause two major clinical presentations: one characterized by fixed, often progressive muscle weakness, and the other by acute, intermittent, and reversible muscle dysfunction manifesting as exercise intolerance (myalgia on exertion, muscle contractures, myoglobinuria). The focus of this review is on recent developments in: clinical features, including a brief description of the newest identified glycogen storage disease type XIII; molecular genetic studies discussing genotype-phenotype correlations in some carbohydrate oxidation disorders; pathophysiological mechanisms, especially those assessed by non-invasive P magnetic resonance spectroscopy; and therapeutic approaches such as nutritional supplementation and gene therapy, including recombinant enzyme replacement. Although major progress has been made in an understanding of the molecular genetic bases of carbohydrate oxidation defects, the pathophysiology of exercise intolerance and muscle weakness remains to be further clarified. Gene therapy and dietary therapeutic regimes appear promising, but need to be actively investigated in the future.

  5. Carbohydrates, Muscle Glycogen, and Improved Performance.

    ERIC Educational Resources Information Center

    Sherman, W. Mike

    1987-01-01

    One way to improve athletic performance without harming the athlete's health is diet manipulation. This article explores the relationship between muscular endurance and muscle glycogen and discusses a diet and training approach to competition. (Author/MT)

  6. Carbohydrate Loading.

    ERIC Educational Resources Information Center

    Csernus, Marilyn

    Carbohydrate loading is a frequently used technique to improve performance by altering an athlete's diet. The objective is to increase glycogen stored in muscles for use in prolonged strenuous exercise. For two to three days, the athlete consumes a diet that is low in carbohydrates and high in fat and protein while continuing to exercise and…

  7. Carbohydrate Loading.

    ERIC Educational Resources Information Center

    Csernus, Marilyn

    Carbohydrate loading is a frequently used technique to improve performance by altering an athlete's diet. The objective is to increase glycogen stored in muscles for use in prolonged strenuous exercise. For two to three days, the athlete consumes a diet that is low in carbohydrates and high in fat and protein while continuing to exercise and…

  8. Fat adaptation science: low-carbohydrate, high- fat diets to alter fuel utilization and promote training adaptation.

    PubMed

    Hawley, John A

    2011-01-01

    The effect of manipulating an individual's habitual diet on skeletal muscle fuel utilization has been of longstanding interest to scientists, and it is now well established that changes in dietary intake that alter the concentration of blood-borne substrates and hormones cause substantial perturbations in the macronutrient storage profile of muscle and exert profound effects on rates of substrate oxidation during exercise. Only recently, however, has it become appreciated that nutrient-exercise interventions can modulate many contraction- induced responses in muscle, and that fuel availability per se provides a 'trigger' for adaptation. Consumption of low-carbohydrate, high- fat diets in the face of endurance training alters patterns of fuel utilization and subsequent exercise responses. Human studies show how low-carbohydrate, fat-rich diets interact with specific contractile stimulus to modulate many of the acute responses to exercise, thereby promoting or inhibiting subsequent training adaptation. Copyright © 2011 S. Karger AG, Basel.

  9. Altered oxidative stress and carbohydrate metabolism in canine mammary tumors

    PubMed Central

    Jayasri, K.; Padmaja, K.; Saibaba, M.

    2016-01-01

    Aim: Mammary tumors are the most prevalent type of neoplasms in canines. Even though cancer induced metabolic alterations are well established, the clinical data describing the metabolic profiles of animal tumors is not available. Hence, our present investigation was carried out with the aim of studying changes in carbohydrate metabolism along with the level of oxidative stress in canine mammary tumors. Materials and Methods: Fresh mammary tumor tissues along with the adjacent healthy tissues were collected from the college surgical ward. The levels of thiobarbituric acid reactive substances (TBARS), glutathione, protein, hexose, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, and glucose-6-phosphate dehydrogenase (G6PD) were analyzed in all the tissues. The results were analyzed statistically. Results: More than two-fold increase in TBARS and three-fold increase in glutathione levels were observed in neoplastic tissues. Hexokinase activity and hexose concentration (175%) was found to be increased, whereas glucose-6-phosphatase (33%), fructose-1, 6-bisphosphatase (42%), and G6PD (5 fold) activities were reduced in tumor mass compared to control. Conclusion: Finally, it was revealed that lipid peroxidation was increased with differentially altered carbohydrate metabolism in canine mammary tumors. PMID:28096627

  10. Altering endogenous carbohydrate availability to support training adaptations.

    PubMed

    Philp, Andrew; Burke, Louise M; Baar, Keith

    2011-01-01

    Glycogen was first identified in muscle over a century and a half ago. Even though we have known of its existence and its role in metabolism for a long time, recognition of its ability to directly and indirectly modulate signaling and the adaptation to exercise is far more recent. Acute exercise induces a number of changes within the body (i.e. sympathetic nervous system activation and elevation of plasma free fatty acids) and muscle (increased AMP-activated protein kinase activity and fat metabolism) that may underlie the long- term adaptation to training. These changes are also affected by glycogen depletion. This review discusses the effect of exercise in a glycogen-depleted state on metabolism and signaling and how this affects the adaptation to exercise. Although 'training low' may increase cellular markers associated with training and enhance functions such as fat oxidation at sub- maximal exercise intensities, how this translates to performance is unclear. Further research is warranted to identify situations both in health and athletic performance where training with low glycogen levels may be beneficial. In the meantime, athletes and coaches need to weigh the pros and cons of training with low carbohydrate within a periodized training program. Copyright © 2011 S. Karger AG, Basel.

  11. Structural alterations of skeletal muscle in copd

    PubMed Central

    Mathur, Sunita; Brooks, Dina; Carvalho, Celso R. F.

    2014-01-01

    Background: Chronic obstructive pulmonary disease (COPD) is a respiratory disease associated with a systemic inflammatory response. Peripheral muscle dysfunction has been well characterized in individuals with COPD and results from a complex interaction between systemic and local factors. Objective: In this narrative review, we will describe muscle wasting in people with COPD, the associated structural changes, muscle regenerative capacity and possible mechanisms for muscle wasting. We will also discuss how structural changes relate to impaired muscle function and mobility in people with COPD. Key Observations: Approximately 30–40% of individuals with COPD experience muscle mass depletion. Furthermore, muscle atrophy is a predictor of physical function and mortality in this population. Associated structural changes include a decreased proportion and size of type-I fibers, reduced oxidative capacity and mitochondrial density mainly in the quadriceps. Observations related to impaired muscle regenerative capacity in individuals with COPD include a lower proportion of central nuclei in the presence or absence of muscle atrophy and decreased maximal telomere length, which has been correlated with reduced muscle cross-sectional area. Potential mechanisms for muscle wasting in COPD may include excessive production of reactive oxygen species (ROS), altered amino acid metabolism and lower expression of peroxisome proliferator-activated receptors-gamma-coactivator 1-alpha mRNA. Despite a moderate relationship between muscle atrophy and function, impairments in oxidative metabolism only seems weakly related to muscle function. Conclusion: This review article demonstrates the cellular modifications in the peripheral muscle of people with COPD and describes the evidence of its relationship to muscle function. Future research will focus on rehabilitation strategies to improve muscle wasting and maximize function. PMID:24678302

  12. Carbohydrates

    MedlinePlus

    ... glossary girlshealth.gov home http://www.girlshealth.gov/ Home Nutrition Nutrition basics Carbohydrates Carbohydrates Carbohydrates (say: kar-boh-HEYE-drayts) are the body's main source of energy. They are sometimes called "carbs" for short. If ...

  13. Altered Pharyngeal Muscles in Parkinson Disease

    PubMed Central

    Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H.; Shill, Holly A.; Caviness, John N.; Samanta, Johan E.; Beach, Thomas G.

    2012-01-01

    Dysphagia (impaired swallowing) is common in Parkinson disease (PD) patients and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor (PC) and cricopharyngeal (CP) sphincter muscles in postmortem specimens from 8 PD and 4 age-matched control patients. Pharyngeal muscles in PD patients exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, the PD patients with dysphagia had a higher percentage of atrophic myofibers vs. with those without dysphagia and controls. The fast-to-slow fiber type transition is consistent with abnormalities in swallowing, slow movement of food and increased tone in the CP sphincter in PD patients. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in PD patients. PMID:22588389

  14. Influence of Post-Exercise Carbohydrate-Protein Ingestion on Muscle Glycogen Metabolism in Recovery and Subsequent Running Exercise.

    PubMed

    Alghannam, Abdullah F; Jedrzejewski, Dawid; Bilzon, James; Thompson, Dylan; Tsintzas, Kostas; Betts, James A

    2016-12-01

    We examined whether carbohydrate-protein ingestion influences muscle glycogen metabolism during short-term recovery from exhaustive treadmill running and subsequent exercise. Six endurance-trained individuals underwent two trials in a randomized double-blind design, each involving an initial run-to-exhaustion at 70% VO2max (Run-1) followed by 4-h recovery (REC) and subsequent run-to-exhaustion at 70% VO2max (Run-2). Carbohydrate-protein (CHO-P; 0.8 g carbohydrate·kg body mass [BM(-1)]·h(-1) plus 0.4 g protein·kg BM(-1)·h(-1)) or isocaloric carbohydrate (CHO; 1.2 g carbohydrate·kg BM(-1)·h(-1)) beverages were ingested at 30-min intervals during recovery. Muscle biopsies were taken upon cessation of Run-1, postrecovery and fatigue in Run-2. Time-to-exhaustion in Run-1 was similar with CHO and CHO-P (81 ± 17 and 84 ± 19 min, respectively). Muscle glycogen concentrations were similar between treatments after Run-1 (99 ± 3 mmol·kg dry mass [dm(-1)]). During REC, muscle glycogen concentrations increased to 252 ± 45 mmol·kg dm(-1) in CHO and 266 ± 30 mmol·kg dm(-1) in CHO-P (p = .44). Muscle glycogen degradation during Run-2 was similar between trials (3.3 ± 1.4 versus 3.5 ± 1.9 mmol·kg dm(-1)·min(-1) in CHO and CHO-P, respectively) and no differences were observed at the respective points of exhaustion (93 ± 21 versus 100 ± 11 mmol·kg dm(-1); CHO and CHO-P, respectively). Similarly, time-to-exhaustion was not different between treatments in Run-2 (51 ± 13 and 49 ± 15 min in CHO and CHO-P, respectively). Carbohydrate-protein ingestion equally accelerates muscle glycogen resynthesis during short-term recovery from exhaustive running as when 1.2 g carbohydrate·kg BM(-1)·h(-1) are ingested. The addition of protein did not alter muscle glycogen utilization or time to fatigue during repeated exhaustive running.

  15. Carbohydrates

    MedlinePlus

    Carbohydrates are one of the main types of nutrients. They are the most important source of energy for your body. Your digestive system changes carbohydrates into glucose (blood sugar). Your body uses this ...

  16. Muscle metabolism during exercise with carbohydrate or protein-carbohydrate ingestion.

    PubMed

    Cermak, Naomi M; Solheim, Amy S; Gardner, Melanie S; Tarnopolsky, Mark A; Gibala, Martin J

    2009-12-01

    Ingesting protein (PRO) with CHO during prolonged exercise is purported to improve performance compared with CHO alone by altering the regulation of skeletal muscle energy provision. However, no study has directly investigated this issue. We tested the hypothesis that compared with CHO alone, coingestion of PRO would alter markers of metabolic control, including the magnitude of glycogen use and the net expansion of the tricarboxylic acid cycle intermediate pool, which has been linked to the capacity for oxidative energy delivery. Eight trained men (mean +/- SE: age = 29 +/- 2 yr; VO2peak = 55 +/- 2 mL x kg(-1) x min(-1)) cycled at 69% +/- 1% VO2peak for 90 min on two occasions, and biopsy samples (vastus lateralis) were obtained before and after exercise. In a randomized, double-blind manner, subjects ingested one of two drinks during exercise that contained either 6% CHO or 6% CHO + 2% PRO (CHO + PRO) at a rate of 1 L x h(-1) to deliver 60 g x h(-1) CHO +/- 20 g x h(-1) PRO. CHO + PRO ingestion increased the plasma concentration of branched chain (561 +/- 46 vs 301 +/- 32 micromol x L(-1)) and essential amino acids (1071 +/- 98 vs 670 +/- 71 micromol x L(-1)) after exercise versus CHO (both P values muscle glycogen use (CHO + PRO = 223 +/- 31 vs CHO = 185 +/- 38 mmol x kg(-1) dry weight) and tricarboxylic acid cycle intermediate expansion (CHO + PRO = 2.3 +/- 0.7 vs CHO = 2.1 +/- 0.2 mmol x kg(-1) dry weight) were similar between trials. Blood creatine kinase activity and 20-km time trial performance measured approximately 24 h after the first exercise bout were not different between treatments. When trained men ingest CHO at a rate on the upper end of the range generally recommended to improve endurance performance, coingestion of PRO does not alter specific markers proposed to reflect an enhanced capacity for skeletal muscle energy delivery.

  17. Carbohydrate feeding speeds reversal of enhanced glucose uptake in muscle after exercise.

    PubMed

    Young, J C; Garthwaite, S M; Bryan, J E; Cartier, L J; Holloszy, J O

    1983-11-01

    Muscle contractile activity results in an increase in glucose uptake rate that can persist for hours. This study was undertaken to determine the effect of carbohydrate repletion on reversal of an exercise-induced increase in glucose uptake. Rats were exercised by swimming. In rats studied 60 min after exercise, muscle glycogen content was 75% depleted and glucose uptake rate was increased. The effect of exercise on glucose uptake was reversed, and glycogen concentration had increased 44 mumol/g muscle, within 18 h in rats fed carbohydrate. In rats fed a carbohydrate-free diet, muscle glycogen increased only 11 mumol/g, and glucose uptake rate had returned only 50% of the way to base line 18 h after exercise. The rate of 3-methylglucose accumulation in muscles was increased sixfold 60 min after exercise. This increase in permeability to sugar was reversed within 18 h in rats fed carbohydrate. In rats fed a carbohydrate-free diet the rate of 3-methylglucose accumulation was still threefold above base line 18 h after exercise. Our results provide evidence that decreased availability of carbohydrate slows reversal of an exercise-induced increase in permeability of muscle to sugar.

  18. Altered muscle activation following hamstring injuries.

    PubMed

    Sole, Gisela; Milosavljevic, Stephan; Nicholson, Helen; Sullivan, S John

    2012-02-01

    The purpose of this study was to compare the electromyographic (EMG) activity of gluteal and thigh muscles of sportspeople with a recent hamstring injury with uninjured controls during a weight-bearing task. Cross-sectional. University laboratory. 16 participants with a hamstring injury (hamstring-injured group, HG) and 18 control participants (control group (CG)) participated in the study. The EMG activity of gluteal, quadriceps and hamstring muscles was recorded during a movement from double- to single-leg movement using surface electrodes. The EMG onsets of biceps femoris and medial hamstrings were significantly earlier for the HG injured and the uninjured sides in preparation for single-leg standing when compared with the CG average. There were no differences in onsets for the gluteal and quadriceps muscles when comparing the injured or uninjured legs of the HG to the bilateral average of the CG. The earlier onset of the injured and the uninjured hamstrings in preparation for single leg stance of the HG in comparison with the CG suggests an alteration in the motor control of these muscles. Altered neuromuscular control following a hamstring injury may be a factor to be considered in the rehabilitation of hamstring injuries.

  19. Neck muscle fatigue alters upper limb proprioception.

    PubMed

    Zabihhosseinian, Mahboobeh; Holmes, Michael W R; Murphy, Bernadette

    2015-05-01

    Limb proprioception is an awareness by the central nervous system (CNS) of the location of a limb in three-dimensional space and is essential for movement and postural control. The CNS uses the position of the head and neck when interpreting the position of the upper limb, and altered input from neck muscles may affect the sensory inputs to the CNS and consequently may impair the awareness of upper limb joint position. The purpose of this study was to determine whether fatigue of the cervical extensors muscles (CEM) using a submaximal fatigue protocol alters the ability to recreate a previously presented elbow angle with the head in a neutral position. Twelve healthy individuals participated. CEM activity was examined bilaterally using surface electromyography, and kinematics of the elbow joint was measured. The fatigue protocol included an isometric neck extension task at 70 % of maximum until failure. Joint position error increased following fatigue, demonstrating a significant main effect of time (F 2, 18 = 19.41, p ≤ 0.0001) for absolute error. No significant differences were found for variable error (F 2, 18 = 0.27, p = 0.76) or constant error (F 2, 18 = 1.16 of time, p ≤ 0.33). This study confirms that fatigue of the CEM can reduce the accuracy of elbow joint position matching. This suggests that altered afferent input from the neck subsequent to fatigue may impair upper limb proprioception.

  20. Carbohydrates.

    PubMed

    Cocinero, Emilio J; Çarçabal, Pierre

    2015-01-01

    Although carbohydrates represent one of the most important families of biomolecules, they remain under-studied in comparison to the other biomolecular families (peptides, nucleobases). Beyond their best-known function of energy source in living systems, they act as mediator of molecular recognition processes, carrying molecular information in the so-called "sugar code," just to name one of their countless functions. Owing to their high conformational flexibility, they encode extremely rich information conveyed via the non-covalent hydrogen bonds within the carbohydrate and with other biomolecular assemblies, such as peptide subunits of proteins. Over the last decade there has been tremendous progress in the study of the conformational preferences of neutral oligosaccharides, and of the interactions between carbohydrates and various molecular partners (water, aromatic models, and peptide models), using vibrational spectroscopy as a sensitive probe. In parallel, other spectroscopic techniques have recently become available to the study of carbohydrates in the gas phase (microwave spectroscopy, IRMPD on charged species).

  1. Alterations in carbohydrate metabolism and its regulation in PPARalpha null mouse hearts

    USDA-ARS?s Scientific Manuscript database

    Although a shift from fatty acids (FAs) to carbohydrates (CHOs) is considered beneficial for the diseased heart, it is unclear why subjects with FA beta-oxidation defects are prone to cardiac decompensation under stress conditions. The present study investigated potential alterations in the myocardi...

  2. Carbohydrate supplementation during prolonged cycling exercise spares muscle glycogen but does not affect intramyocellular lipid use.

    PubMed

    Stellingwerff, Trent; Boon, Hanneke; Gijsen, Annemie P; Stegen, Jos H C H; Kuipers, Harm; van Loon, Luc J C

    2007-07-01

    Using contemporary stable-isotope methodology and fluorescence microscopy, we assessed the impact of carbohydrate supplementation on whole-body and fiber-type-specific intramyocellular triacylglycerol (IMTG) and glycogen use during prolonged endurance exercise. Ten endurance-trained male subjects were studied twice during 3 h of cycling at 63 +/- 4% of maximal O(2) uptake with either glucose ingestion (CHO trial; 0.7 g CHO kg(-1) h(-1)) or without (CON placebo trial; water only). Continuous infusions with [U-(13)C] palmitate and [6,6-(2)H(2)] glucose were applied to quantify plasma free fatty acids (FFA) and glucose oxidation rates and to estimate intramyocellular lipid and glycogen use. Before and after exercise, muscle biopsy samples were taken to quantify fiber-type-specific IMTG and glycogen content. Plasma glucose rate of appearance (R (a)) and carbohydrate oxidation rates were substantially greater in the CHO vs CON trial. Carbohydrate supplementation resulted in a lower muscle glycogen use during the first hour of exercise in the CHO vs CON trial, resulting in a 38 +/- 19 and 57 +/- 22% decreased utilization in type I and II muscle-fiber glycogen content, respectively. In the CHO trial, both plasma FFA R (a) and subsequent plasma FFA concentrations were lower, resulting in a 34 +/- 12% reduction in plasma FFA oxidation rates during exercise (P < 0.05). Carbohydrate intake did not augment IMTG utilization, as fluorescence microscopy revealed a 76 +/- 21 and 78 +/- 22% reduction in type I muscle-fiber lipid content in the CHO and CON trial, respectively. We conclude that carbohydrate supplementation during prolonged cycling exercise does not modulate IMTG use but spares muscle glycogen use during the initial stages of exercise in endurance-trained men.

  3. Increasing skeletal muscle carnitine availability does not alter the adaptations to high-intensity interval training.

    PubMed

    Shannon, Christopher E; Ghasemi, Reza; Greenhaff, Paul L; Stephens, Francis B

    2017-03-27

    Increasing skeletal muscle carnitine availability alters muscle metabolism during steady-state exercise in healthy humans. We investigated whether elevating muscle carnitine, and thereby the acetyl-group buffering capacity, altered the metabolic and physiological adaptations to 24 weeks of high-intensity interval training (HIIT) at 100% maximal exercise capacity (Wattmax ). Twenty-one healthy male volunteers (age 23±2 years; BMI 24.2±1.1 kg/m(2) ) performed 2x3 minute bouts of cycling exercise at 100% Wattmax , separated by five minutes rest. Fourteen volunteers repeated this protocol following 24 weeks of HIIT and twice-daily consumption of 80g carbohydrate (CON) or 3g L-carnitine+carbohydrate (CARN). Before HIIT, muscle phosphocreatine (PCr) degradation (P<0.0001), glycogenolysis (P<0.0005), PDC activation (P<0.05), and acetylcarnitine (P<0.005) were 2.3, 2.1, 1.5 and 1.5-fold greater, respectively, in exercise bout two compared to bout one, whilst lactate accumulation tended (P<0.07) to be 1.5-fold greater. Following HIIT, muscle free carnitine was 30% greater in CARN vs CON at rest and remained 40% elevated prior to the start of bout two (P<0.05). Following bout two, free carnitine content, PCr degradation, glycogenolysis, lactate accumulation, and PDC activation were all similar between CON and CARN, albeit markedly lower than before HIIT. VO2max , Wattmax and work-output were similarly increased in CON and CARN, by 9, 15 and 23% (P<0.001). In summary, increased reliance on non-mitochondrial ATP resynthesis during a second bout of intense exercise is accompanied by increased carnitine acetylation. Augmenting muscle carnitine during 24 weeks of HIIT did not alter this, nor enhance muscle metabolic adaptations or performance gains beyond those with HIIT alone. This article is protected by copyright. All rights reserved.

  4. Carbohydrate ingestion and muscle glycogen depletion during marathon and ultramarathon racing.

    PubMed

    Noakes, T D; Lambert, E V; Lambert, M I; McArthur, P S; Myburgh, K H; Benade, A J

    1988-01-01

    Two studies were undertaken to characterize the effects of carbohydrate ingestion on fuel/hormone response to exercise and muscle glycogen utilization during prolonged competitive exercise. In study 1, eighteen subjects were divided into three groups, matched for maximum oxygen consumption (VO2max) and blood lactate turnpoint. All subjects underwent a 3-day carbohydrate (CHO) depletion phase, followed by 3 days of CHO loading (500-600 g.day-1). During the race, the groups drank either 2% glucose (G), 8% glucose polymer (GP), or 8% fructose (F). Muscle biopsies were performed before and after the race and venous blood was sampled before and at regular intervals during the race. In study 2, eighteen subjects divided into 2 matched groups ingested either a 4% G or 10% GP solution during a 56 km race. Despite significantly greater CHO ingestion by GP and F in study 1 and by GP in study 2, blood glucose, free fatty acids and insulin concentrations, muscle glycogen utilization and running performance were not different between groups. These studies show (i) that hypoglycaemia is uncommon in athletes competing in races of up to 56 km provided they CHO-load before and ingest a minimum of 10 g CHO.h-1 during competition; (ii) that neither the amount (10 g vs 40 g.h-1) nor the type of carbohydrate (G vs GP vs F) has any effect on the extent of muscle glycogen depletion or running performance in matched subjects racing over distances up to 56 km.

  5. Carbohydrate coingestion delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion.

    PubMed

    Gorissen, Stefan H M; Burd, Nicholas A; Hamer, Henrike M; Gijsen, Annemie P; Groen, Bart B; van Loon, Luc J C

    2014-06-01

    Dietary protein digestion and absorption is an important factor modulating muscle protein accretion. However, there are few data available on the effects of coingesting other macronutrients with protein on digestion and absorption kinetics and the subsequent muscle protein synthetic response. The objective of the study was to determine the impact of carbohydrate coingestion with protein on dietary protein digestion and absorption and muscle protein accretion in healthy young and older men. Twenty-four healthy young (aged 21± 1 y, body mass index 21.8 ±0.5 kg/m(2)) and 25 older (aged 75 ± 1 y, body mass index 25.4 ± 0.6 kg/m(2)) men received a primed continuous L-[ring-(2)H5]-phenylalanine and L-[ring-3,5-(2)H2]-tyrosine infusion and ingested 20 g intrinsically L-[1-(13)C]-phenylalanine-labeled protein with (Pro+CHO) or without (Pro) 60 g carbohydrate. Plasma samples and muscle biopsies were collected in a postabsorptive and postprandial state. Carbohydrate coingestion delayed the appearance of exogenous phenylalanine in the circulation (P = .001). Dietary protein-derived phenylalanine availability over the 5-hour postprandial period was lower in the older (62 ± 2%) when compared with the young subjects (74 ± 2%; P = .007), with no differences between conditions (P = .20). Carbohydrate coingestion did not modulate postprandial muscle protein synthesis rates (0.035 ± 0.003 vs 0.043 ± 0.004 and 0.033 ± 0.002 vs 0.035 ± 0.003%/h after Pro vs Pro+CHO in the young and older group, respectively). In accordance, no differences in muscle protein-bound L-[1-(13)C]-phenylalanine enrichments were observed between conditions (0.020 ± 0.002 vs 0.020 ± 0.002 and 0.019 ± 0.003 vs 0.022 ± 0.004 mole percent excess after Pro vs Pro+CHO in the young and older subjects, respectively). Carbohydrate coingestion with protein delays dietary protein digestion and absorption but does not modulate postprandial muscle protein accretion in healthy young or older men.

  6. Muscle glycogen utilisation during Rugby match play: Effects of pre-game carbohydrate.

    PubMed

    Bradley, Warren J; Morehen, James C; Haigh, Julian; Clarke, Jon; Donovan, Timothy F; Twist, Craig; Cotton, Caroline; Shepherd, Sam; Cocks, Matthew; Sharma, Asheesh; Impey, Samuel G; Cooper, Robert G; Maclaren, Don P M; Morton, James P; Close, Graeme L

    2016-12-01

    Although the physical demands of Rugby League (RL) match-play are well-known, the fuel sources supporting energy-production are poorly understood. We therefore assessed muscle glycogen utilisation and plasma metabolite responses to RL match-play after a relatively high (HCHO) or relatively low CHO (LCHO) diet. Sixteen (mean±SD age; 18±1 years, body-mass; 88±12kg, height 180±8cm) professional players completed a RL match after 36-h consuming a non-isocaloric high carbohydrate (n=8; 6gkgday(-1)) or low carbohydrate (n=8; 3gkgday(-1)) diet. Muscle biopsies and blood samples were obtained pre- and post-match, alongside external and internal loads quantified using Global Positioning System technology and heart rate, respectively. Data were analysed using effects sizes ±90% CI and magnitude-based inferences. Differences in pre-match muscle glycogen between high and low carbohydrate conditions (449±51 and 444±81mmolkg(-1)d.w.) were unclear. High (243±43mmolkg(-1)d.w.) and low carbohydrate groups (298±130mmolkg(-1)d.w.) were most and very likely reduced post-match, respectively. For both groups, differences in pre-match NEFA and glycerol were unclear, with a most likely increase in NEFA and glycerol post-match. NEFA was likely lower in the high compared with low carbohydrate group post-match (0.95±0.39mmoll(-1) and 1.45±0.51mmoll(-1), respectively), whereas differences between the 2 groups for glycerol were unclear (98.1±33.6mmoll(-1) and 123.1±39.6mmoll(-1)) in the high and low carbohydrate groups, respectively. Professional RL players can utilise ∼40% of their muscle glycogen during a competitive match regardless of their carbohydrate consumption in the preceding 36-h. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  7. Adrenaline increases skeletal muscle glycogenolysis, pyruvate dehydrogenase activation and carbohydrate oxidation during moderate exercise in humans

    PubMed Central

    Watt, Matthew J; Howlett, Kirsten F; Febbraio, Mark A; Spriet, Lawrence L; Hargreaves, Mark

    2001-01-01

    To evaluate the role of adrenaline in regulating carbohydrate metabolism during moderate exercise, 10 moderately trained men completed two 20 min exercise bouts at 58 ± 2 % peak pulmonary oxygen uptake (V̇O2,peak). On one occasion saline was infused (CON), and on the other adrenaline was infused intravenously for 5 min prior to and throughout exercise (ADR). Glucose kinetics were measured by a primed, continuous infusion of 6,6-[2H]glucose and muscle samples were obtained prior to and at 1 and 20 min of exercise. The infusion of adrenaline elevated (P < 0.01) plasma adrenaline concentrations at rest (pre-infusion, 0.28 ± 0.09; post-infusion, 1.70 ± 0.45 nmol l−1; means ±s.e.m.) and this effect was maintained throughout exercise. Total carbohydrate oxidation increased by 18 % and this effect was due to greater skeletal muscle glycogenolysis (P < 0.05) and pyruvate dehydrogenase (PDH) activation (P < 0.05, treatment effect). Glucose rate of appearance was not different between trials, but the infusion of adrenaline decreased (P < 0.05, treatment effect) skeletal muscle glucose uptake in ADR. During exercise muscle glucose 6-phosphate (G-6-P) (P = 0.055, treatment effect) and lactate (P < 0.05) were elevated in ADR compared with CON and no changes were observed for pyruvate, creatine, phosphocreatine, ATP and the calculated free concentrations of ADP and AMP. The data demonstrate that elevated plasma adrenaline levels during moderate exercise in untrained men increase skeletal muscle glycogen breakdown and PDH activation, which results in greater carbohydrate oxidation. The greater muscle glycogenolysis appears to be due to increased glycogen phosphorylase transformation whilst the increased PDH activity cannot be readily explained. Finally, the decreased glucose uptake observed during exercise in ADR is likely to be due to the increased intracellular G-6-P and a subsequent decrease in glucose phosphorylation. PMID:11433007

  8. The influence of altered gravity on carbohydrate metabolism in excised wheat leaves

    NASA Technical Reports Server (NTRS)

    Obenland, D. M.; Brown, C. S.

    1994-01-01

    We developed a system to study the influence of altered gravity on carbohydrate metabolism in excised wheat leaves by means of clinorotation. The use of excised leaves in our clinostat studies offered a number of advantages over the use of whole plants, most important of which were minimization of exogenous mechanical stress and a greater amount of carbohydrate accumulation during the time of treatment. We found that horizontal clinorotation of excised wheat leaves resulted in significant reductions in the accumulation of fructose, sucrose, starch and fructan relative to control, vertically clinorotated leaves. Photosynthesis, dark respiration and the extractable activities of ADP glucose pyrophosphorylase (EC 2.7.7.27), sucrose phosphate synthase (EC 2.4.4.14), sucrose sucrose fructosyltransferase (EC 2.4.1.99), and fructan hydrolase (EC 3.2.1.80) were unchanged due to altered gravity treatment.

  9. The influence of altered gravity on carbohydrate metabolism in excised wheat leaves

    NASA Technical Reports Server (NTRS)

    Obenland, D. M.; Brown, C. S.

    1994-01-01

    We developed a system to study the influence of altered gravity on carbohydrate metabolism in excised wheat leaves by means of clinorotation. The use of excised leaves in our clinostat studies offered a number of advantages over the use of whole plants, most important of which were minimization of exogenous mechanical stress and a greater amount of carbohydrate accumulation during the time of treatment. We found that horizontal clinorotation of excised wheat leaves resulted in significant reductions in the accumulation of fructose, sucrose, starch and fructan relative to control, vertically clinorotated leaves. Photosynthesis, dark respiration and the extractable activities of ADP glucose pyrophosphorylase (EC 2.7.7.27), sucrose phosphate synthase (EC 2.4.4.14), sucrose sucrose fructosyltransferase (EC 2.4.1.99), and fructan hydrolase (EC 3.2.1.80) were unchanged due to altered gravity treatment.

  10. beta-adrenergic effects on carbohydrate metabolism in the unweighted rat soleus muscle

    NASA Technical Reports Server (NTRS)

    Kirby, Christopher R.; Tischler, Marc E.

    1990-01-01

    The effect of unweighting on the response of the soleus-muscle carbohydrate metabolism to a beta-adrenergic agonist (isoproterenol) was investigated in rats that were subjected to three days of tail-cast suspension. It was found that isoproterenol promoted glycogen degradation in soleus from suspended rats to a higher degree than in weighted soleus from control rats, and had no effect in unweighted digitorum longus. However, isoproterenol did not have a greater inhibitory effect on the net uptake of tritium-labeled 2-deoxy-glucose by the unweighted soleus and that isoproterenol inhibited hexose phosphorylation less in the unweighted than in the control muscle.

  11. Effect of altering starting length and activation timing of muscle on fiber strain and muscle damage.

    PubMed

    Butterfield, Timothy A; Herzog, Walter

    2006-05-01

    Muscle strain injuries are some of the most frequent injuries in sports and command a great deal of attention in an effort to understand their etiology. These injuries may be the culmination of a series of subcellular events accumulated through repetitive lengthening (eccentric) contractions during exercise, and they may be influenced by a variety of variables including fiber strain magnitude, peak joint torque, and starting muscle length. To assess the influence of these variables on muscle injury magnitude in vivo, we measured fiber dynamics and joint torque production during repeated stretch-shortening cycles in the rabbit tibialis anterior muscle, at short and long muscle lengths, while varying the timing of activation before muscle stretch. We found that a muscle subjected to repeated stretch-shortening cycles of constant muscle-tendon unit excursion exhibits significantly different joint torque and fiber strains when the timing of activation or starting muscle length is changed. In particular, measures of fiber strain and muscle injury were significantly increased by altering activation timing and increasing the starting length of the muscle. However, we observed differential effects on peak joint torque during the cyclic stretch-shortening exercise, as increasing the starting length of the muscle did not increase torque production. We conclude that altering activation timing and muscle length before stretch may influence muscle injury by significantly increasing fiber strain magnitude and that fiber dynamics is a more important variable than muscle-tendon unit dynamics and torque production in influencing the magnitude of muscle injury.

  12. Long-Term Warming Alters Carbohydrate Degradation Potential in Temperate Forest Soils.

    PubMed

    Pold, Grace; Billings, Andrew F; Blanchard, Jeff L; Burkhardt, Daniel B; Frey, Serita D; Melillo, Jerry M; Schnabel, Julia; van Diepen, Linda T A; DeAngelis, Kristen M

    2016-11-15

    As Earth's climate warms, soil carbon pools and the microbial communities that process them may change, altering the way in which carbon is recycled in soil. In this study, we used a combination of metagenomics and bacterial cultivation to evaluate the hypothesis that experimentally raising soil temperatures by 5°C for 5, 8, or 20 years increased the potential for temperate forest soil microbial communities to degrade carbohydrates. Warming decreased the proportion of carbohydrate-degrading genes in the organic horizon derived from eukaryotes and increased the fraction of genes in the mineral soil associated with Actinobacteria in all studies. Genes associated with carbohydrate degradation increased in the organic horizon after 5 years of warming but had decreased in the organic horizon after warming the soil continuously for 20 years. However, a greater proportion of the 295 bacteria from 6 phyla (10 classes, 14 orders, and 34 families) isolated from heated plots in the 20-year experiment were able to depolymerize cellulose and xylan than bacterial isolates from control soils. Together, these findings indicate that the enrichment of bacteria capable of degrading carbohydrates could be important for accelerated carbon cycling in a warmer world.

  13. Effects of dietary carbohydrate on delayed onset muscle soreness and reactive oxygen species after contraction induced muscle damage

    PubMed Central

    Close, G; Ashton, T; Cable, T; Doran, D; Noyes, C; McArdle, F; MacLaren, D

    2005-01-01

    Background: Delayed onset muscle soreness (DOMS) occurs after unaccustomed exercise and has been suggested to be attributable to reactive oxygen species (ROS). Previous studies have shown increased ROS after lengthening contractions, attributable to invading phagocytes. Plasma glucose is a vital fuel for phagocytes, therefore carbohydrate (CHO) status before exercise may influence ROS production and DOMS Objective: To examine the effect of pre-exercise CHO status on DOMS, ROS production, and muscle function after contraction induced muscle damage. Method: Twelve subjects performed two downhill runs, one after a high CHO diet and one after a low CHO diet. Blood samples were drawn for analysis of malondialdehyde, total glutathione, creatine kinase, non-esterified fatty acids, lactate, glucose, and leucocytes. DOMS and muscle function were assessed daily. Results: The high CHO diet resulted in higher respiratory exchange ratio and lactate concentrations than the low CHO diet before exercise. The low CHO diet resulted in higher non-esterified fatty acid concentrations before exercise. DOMS developed after exercise and remained for up to 96 hours, after both diets. A biphasic response in creatine kinase occurred after both diets at 24 and 96 hours after exercise. Malondialdehyde had increased 72 hours after exercise after both diets, and muscle function was attenuated up to this time. Conclusions: Downhill running resulted in increased ROS production and ratings of DOMS and secondary increases in muscle damage. CHO status before exercise had no effect. PMID:16306505

  14. Oxidative proteome alterations during skeletal muscle ageing

    PubMed Central

    Lourenço dos Santos, Sofia; Baraibar, Martin A.; Lundberg, Staffan; Eeg-Olofsson, Orvar; Larsson, Lars; Friguet, Bertrand

    2015-01-01

    Sarcopenia corresponds to the degenerative loss of skeletal muscle mass, quality, and strength associated with ageing and leads to a progressive impairment of mobility and quality of life. However, the cellular and molecular mechanisms involved in this process are not completely understood. A hallmark of cellular and tissular ageing is the accumulation of oxidatively modified (carbonylated) proteins, leading to a decreased quality of the cellular proteome that could directly impact on normal cellular functions. Although increased oxidative stress has been reported during skeletal muscle ageing, the oxidized protein targets, also referred as to the ‘oxi-proteome’ or ‘carbonylome’, have not been characterized yet. To better understand the mechanisms by which these damaged proteins build up and potentially affect muscle function, proteins targeted by these modifications have been identified in human rectus abdominis muscle obtained from young and old healthy donors using a bi-dimensional gel electrophoresis-based proteomic approach coupled with immunodetection of carbonylated proteins. Among evidenced protein spots, 17 were found as increased carbonylated in biopsies from old donors comparing to young counterparts. These proteins are involved in key cellular functions such as cellular morphology and transport, muscle contraction and energy metabolism. Importantly, impairment of these pathways has been described in skeletal muscle during ageing. Functional decline of these proteins due to irreversible oxidation may therefore impact directly on the above-mentioned pathways, hence contributing to the generation of the sarcopenic phenotype. PMID:26073261

  15. Oxidative proteome alterations during skeletal muscle ageing.

    PubMed

    Lourenço dos Santos, Sofia; Baraibar, Martin A; Lundberg, Staffan; Eeg-Olofsson, Orvar; Larsson, Lars; Friguet, Bertrand

    2015-08-01

    Sarcopenia corresponds to the degenerative loss of skeletal muscle mass, quality, and strength associated with ageing and leads to a progressive impairment of mobility and quality of life. However, the cellular and molecular mechanisms involved in this process are not completely understood. A hallmark of cellular and tissular ageing is the accumulation of oxidatively modified (carbonylated) proteins, leading to a decreased quality of the cellular proteome that could directly impact on normal cellular functions. Although increased oxidative stress has been reported during skeletal muscle ageing, the oxidized protein targets, also referred as to the 'oxi-proteome' or 'carbonylome', have not been characterized yet. To better understand the mechanisms by which these damaged proteins build up and potentially affect muscle function, proteins targeted by these modifications have been identified in human rectus abdominis muscle obtained from young and old healthy donors using a bi-dimensional gel electrophoresis-based proteomic approach coupled with immunodetection of carbonylated proteins. Among evidenced protein spots, 17 were found as increased carbonylated in biopsies from old donors comparing to young counterparts. These proteins are involved in key cellular functions such as cellular morphology and transport, muscle contraction and energy metabolism. Importantly, impairment of these pathways has been described in skeletal muscle during ageing. Functional decline of these proteins due to irreversible oxidation may therefore impact directly on the above-mentioned pathways, hence contributing to the generation of the sarcopenic phenotype.

  16. Changes of Dietary Fat and Carbohydrate Content Alter Central and Peripheral Clock in Humans.

    PubMed

    Pivovarova, Olga; Jürchott, Karsten; Rudovich, Natalia; Hornemann, Silke; Ye, Lu; Möckel, Simona; Murahovschi, Veronica; Kessler, Katharina; Seltmann, Anne-Cathrin; Maser-Gluth, Christiane; Mazuch, Jeannine; Kruse, Michael; Busjahn, Andreas; Kramer, Achim; Pfeiffer, Andreas F H

    2015-06-01

    The circadian clock coordinates numerous metabolic processes with light-dark and feeding regimens. However, in humans it is unknown whether dietary patterns influence circadian rhythms. We examined the effects of switching from a high-carbohydrate, low-fat diet to a low-carbohydrate, high fat (LC/HFD) isocaloric diet on the central and peripheral circadian clocks in humans. Diurnal patterns of salivary cortisol and gene expression were analyzed in blood monocytes of 29 nonobese healthy subjects before and 1 and 6 weeks after the dietary switch. For this, we established a method of rhythm prediction by 3-time point data. The centrally driven cortisol rhythm showed a phase delay 1 and 6 weeks after the dietary switch to a LC/HFD as well as an amplitude increase. The dietary switch altered diurnal oscillations of core clock genes (PER1, PER2, PER3, and TEF) and inflammatory genes (CD14, CD180, NFKBIA, and IL1B). The LC/HFD also affected the expression of nonoscillating genes contributing to energy metabolism (SIRT1) and fat metabolism (ACOX3 and IDH3A). Expression of clock genes but not of salivary cortisol in monocytes tightly correlated with levels of blood lipids and with expression of metabolic and inflammatory genes. Our results suggest that the modulation of the dietary fat and carbohydrate content alters the function of the central and peripheral circadian clocks in humans.

  17. Renal function alterations during skeletal muscle disuse in simulated microgravity

    NASA Technical Reports Server (NTRS)

    Tucker, Bryan J.

    1992-01-01

    This project was to examine the alterations in renal functions during skeletal muscle disuse in simulated microgravity. Although this area could cover a wide range of investigative efforts, the limited funding resulted in the selection of two projects. These projects would result in data contributing to an area of research deemed high priority by NASA and would address issues of the alterations in renal response to vasoactive stimuli during conditions of skeletal muscle disuse as well as investigate the contribution of skeletal muscle disuse, conditions normally found in long term human exposure to microgravity, to the balance of fluid and macromolecules within the vasculature versus the interstitium. These two projects selected are as follows: investigate the role of angiotensin 2 on renal function during periods of simulated microgravity and skeletal muscle disuse to determine if the renal response is altered to changes in circulating concentrations of angiotensin 2 compared to appropriate controls; and determine if the shift of fluid balance from vasculature to the interstitium, the two components of extracellular fluid volume, that occur during prolonged exposure to microgravity and skeletal muscle disuse is a result, in part, to alterations in the fluid and macromolecular balance in the peripheral capillary beds, of which the skeletal muscle contains the majority of recruitment capillaries. A recruitment capillary bed would be most sensitive to alterations in Starling forces and fluid and macromolecular permeability.

  18. Attenuation of Helicteres isora L. bark extracts on streptozotocin-induced alterations in glycogen and carbohydrate metabolism in albino rats.

    PubMed

    Kumar, G; Sharmila Banu, G; Murugesan, A G

    2009-11-01

    The present study was undertaken to assess the effect of Helicteres isora L. on four important enzymes of carbohydrate metabolism (glucokinase [GK], hexokinase [HK] phosphofructokinase [PFK] and fructose-1, 6-bisphosphatase [FBP]) along with glycogen content of insulin-dependent (skeletal muscle and liver) and insulin-independent tissues (kidneys and brain) in streptozotocin (STZ; 60 mg/kg)-induced model of diabetes for 30 days. Administration of bark extracts (100, 200 mg/kg) for 30 days led to decrease in plasma glucose levels by approximately 9.60% and 22.04% and 19.18% and 33.93% on 15th and 30th day, respectively, of the experiment. Liver and two-kidney weight expressed as percentage of body weight significantly increased in diabetics (P < 0.05) versus normal controls. Renal glycogen content increased by 10 folds while hepatic and skeletal muscle glycogen content decreased by 75% and 68% in diabetic controls versus controls. H. isora did not affect glycogen content in any tissue. The decreased activities of PFK, GK, FBP and HK in diabetic controls were 40%, 50%, 50% and 60% and bark extract of H. isora partially corrected this alteration. The efficacy of the bark extract was comparable with Tolbutamide, a well-known hypoglycemic drug.

  19. Effect of various ratios of carbohydrate-protein supplementation on resistance exercise-induced muscle damage.

    PubMed

    Samadi, A; Gaeini, A A; Kordi, M R; Rahimi, M; Rahnama, N; Bambaeichi, E

    2012-04-01

    Previous studies have indicated that exercise-induced muscle damage might be attenuated by coingestion of protein and carbohydrate supplement. The purpose of this study was to compare the effect of three various ratios of carbohydrate-protein (CHO+PRO) supplements on resistance exercise-induced muscle damage indices. Twenty-eight untrained male students voluntarily participated in this study and were randomly assigned to one of the four groups: 1) CHO+PRO 2:1 ratio, N.=7; 2) CHO+PRO 3:1 ratio, N.=8; 3) CHO+PRO 4:1 ratio, N.=7; 4) placebo group, N.=6. They performed a single bout of resistance exercise (whole body: 3 set×8-10 reps with 70-75% 1RM), with eccentric concentration. Every group consumed prepared CHO/PRO beverages (9% concentration, 10 mL/kg/bw-1 at different ratios) or the same amount of placebo beverage before and in 15 min intervals during exercise. Blood samples were taken before the exercise bout and also at 1 and 24 h post-exercise. In addition, muscle soreness scores were recorded before and 1, 24, and 48 h postexercise. Repeated measures ANOVA (between-within design) and Bonferroni post hoc test were used to analyze dependent measures (α=0.05). Serum creatine kinase (CK) and myoglobin (Mb) increased in all groups compared with pre-exercise but the significant difference among groups was observed in 24 h postexercise, in a way that both CK and Mb levels were higher in placebo group. Muscle soreness increased for all groups from pre to postexercise, but there was not any significant difference among groups at any time point. Findings of this study showed that CHO+PRO decreased serum CK and Mb at 24 h post exercise, but did not affect muscle soreness at any time points after exercise. Moreover, there were no significant differences between various ratios of CHO-PRO supplementation.

  20. Fiber type-specific muscle glycogen sparing due to carbohydrate intake before and during exercise.

    PubMed

    De Bock, K; Derave, W; Ramaekers, M; Richter, E A; Hespel, P

    2007-01-01

    The effect of carbohydrate intake before and during exercise on muscle glycogen content was investigated. According to a randomized crossover study design, eight young healthy volunteers (n = 8) participated in two experimental sessions with an interval of 3 wk. In each session subjects performed 2 h of constant-load bicycle exercise ( approximately 75% maximal oxygen uptake). On one occasion (CHO), they received carbohydrates before ( approximately 150 g) and during (1 g.kg body weight(-1).h(-1)) exercise. On the other occasion they exercised after an overnight fast (F). Fiber type-specific relative glycogen content was determined by periodic acid Schiff staining combined with immunofluorescence in needle biopsies from the vastus lateralis muscle before and immediately after exercise. Preexercise glycogen content was higher in type IIa fibers [9.1 +/- 1 x 10(-2) optical density (OD)/microm(2)] than in type I fibers (8.0 +/- 1 x 10(-2) OD/microm(2); P < 0.0001). Type IIa fiber glycogen content decreased during F from 9.6 +/- 1 x 10(-2) OD/microm(2) to 4.5 +/- 1 x 10(-2) OD/microm(2) (P = 0.001), but it did not significantly change during CHO (P = 0.29). Conversely, in type I fibers during CHO and F the exercise bout decreased glycogen content to the same degree. We conclude that the combination of carbohydrate intake both before and during moderate- to high-intensity endurance exercise results in glycogen sparing in type IIa muscle fibers.

  1. Regulatory role of zinc during aluminium-induced altered carbohydrate metabolism in rat brain.

    PubMed

    Singla, Neha; Dhawan, D K

    2012-03-01

    Aluminium is considered an environmental neurotoxicant and causes many neurological disorders, whereas zinc is vital for many biological functions. The present study was carried out to investigate the role of Zn, if any, in mitigating the adverse effects inflicted by Al on carbohydrate metabolism in rat brain. Male Sprague-Dawley rats weighing 140-160 g were divided into four different groups: normal control, Al-treated (100 mg/kg b.w./day in drinking water via oral gavage), Zn-treated (227mg/liter in drinking water), and combined Al- and Zn-treated rats. All the treatments were continued for 2 months, and their effects on carbohydrate-metabolizing enzymes were studied. Additionally, expressions of the proteins glycogen synthase kinase-3 (GSK3) and protein phosphatase (PP1), which help in regulating carbohydrate energy metabolism, were also studied. Al treatment resulted in increased activities of the glucose-6-phosphatase (G6P), glucose-6-isomerase (G6I), and lactate dehydrogenase (LDH), whereas the activities of hexokinase and succinate dehydrogenase (SDH) and glycogen content were decreased. Moreover, no significant change was observed in the biochemical parameters upon Zn supplementation alone. However, Zn supplementation to Al-treated rats was able to reduce significantly the Al-induced increased activities of G6P, G6I, and LDH, but it elevated the levels of hexokinase, SDH, and glycogen. Furthermore, Al treatment increased the protein expression of GSK3 and decreased the PP1 expression, which were found to be reversed upon Zn administration. Hence, Zn is effective in regulating theAl-induced alterations in carbohydrate metabolism. Copyright © 2011 Wiley Periodicals, Inc.

  2. Ultrastructural alterations in skeletal muscle fibers of rats after exercise

    NASA Technical Reports Server (NTRS)

    Akuzawa, M.; Hataya, M.

    1982-01-01

    Ultrastructural alterations in skeletal muscle fibers were electron microscopically studied in rats forced to run on the treadmill until all-out. When they were mild and limited to relatively small areas, the reconstruction of filaments ensued within 10 days without infiltration of cells. When they were severe and extensive, phagocytes infiltrated in the lesions and removed degenerative sacroplasmic debris from muscle fibers. A little later, myoblasts appeared and regeneration was accomplished in 30 days in much the same manner as in myogenesis.

  3. Alterations in contractile properties of tongue muscles in old rats.

    PubMed

    Ota, Fumikazu; Connor, Nadine P; Konopacki, Richard

    2005-10-01

    Fatigue and weakness are well-known signs of aging that are related to sarcopenia, or loss of skeletal muscle mass, organization, and strength. Sarcopenia may affect swallowing. The tongue plays a vital role in swallowing, but there is limited knowledge regarding age-related changes in lingual muscle contractile properties. Our purpose was to determine whether alterations in tongue force, temporal features of tongue muscle contraction, and fatigability are manifested as a function of aging in old rats. We evaluated tongue muscle contractile properties in young and old Fischer 344/Brown Norway rats. Contractions were elicited via bilateral electrical stimulation of the hypoglossal nerves. Maximum tongue forces and fatigability were not significantly altered in old animals, but aging was associated with significantly longer twitch contraction time and longer half-decay recovery time intervals (p < .01). The results indicated that old animals generated sufficient maximum tongue forces, but were slower in achieving these forces than young animals. These findings are consistent with reports of altered temporal parameters of tongue actions during swallowing in humans, and suggest that a disruption in the timing of muscle contraction onset and recovery may contribute to the altered tongue kinetics observed with aging.

  4. Bex1 knock out mice show altered skeletal muscle regeneration

    PubMed Central

    Koo, Jae Hyung; Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

    2008-01-01

    Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca2+/CaM may be involved in skeletal muscle regeneration. PMID:17884015

  5. Bex1 knock out mice show altered skeletal muscle regeneration

    SciTech Connect

    Koo, Jae Hyung Smiley, Mark A.; Lovering, Richard M.; Margolis, Frank L.

    2007-11-16

    Bex1 and Calmodulin (CaM) are upregulated during skeletal muscle regeneration. We confirm this finding and demonstrate the novel finding that they interact in a calcium-dependent manner. To study the role of Bex1 and its interaction with CaM in skeletal muscle regeneration, we generated Bex1 knock out (Bex1-KO) mice. These mice appeared to develop normally and are fertile, but displayed a functional deficit in exercise performance compared to wild type (WT) mice. After intramuscular injection of cardiotoxin, which causes extensive and reproducible myotrauma followed by recovery, regenerating muscles of Bex1-KO mice exhibited elevated and prolonged cell proliferation, as well as delayed cell differentiation, compared to WT mice. Thus, our results provide the first evidence that Bex1-KO mice show altered muscle regeneration, and allow us to propose that the interaction of Bex1 with Ca{sup 2+}/CaM may be involved in skeletal muscle regeneration.

  6. A Comparative Study of N-glycolylneuraminic Acid (Neu5Gc) and Cytotoxic T Cell (CT) Carbohydrate Expression in Normal and Dystrophin-Deficient Dog and Human Skeletal Muscle

    PubMed Central

    Martin, Paul T.; Golden, Bethannie; Okerblom, Jonathan; Camboni, Marybeth; Chandrasekharan, Kumaran; Xu, Rui; Varki, Ajit; Flanigan, Kevin M.; Kornegay, Joe N.

    2014-01-01

    The expression of N-glycolylneuraminic acid (Neu5Gc) and the cytotoxic T cell (CT) carbohydrate can impact the severity of muscular dystrophy arising from the loss of dystrophin in mdx mice. Here, we describe the expression of these two glycans in skeletal muscles of dogs and humans with or without dystrophin-deficiency. Neu5Gc expression was highly reduced (>95%) in muscle from normal golden retriever crosses (GR, n = 3) and from golden retriever with muscular dystrophy (GRMD, n = 5) dogs at multiple ages (3, 6 and 13 months) when compared to mouse muscle, however, overall sialic acid expression in GR and GRMD muscles remained high at all ages. Neu5Gc was expressed on only a minority of GRMD satellite cells, CD8+ T lymphocytes and macrophages. Human muscle from normal (no evident disease, n = 3), Becker (BMD, n = 3) and Duchenne (DMD, n = 3) muscular dystrophy individuals had absent to very low Neu5Gc staining, but some punctate intracellular muscle staining was present in BMD and DMD muscles. The CT carbohydrate was localized to the neuromuscular junction in GR muscle, while GRMD muscles had increased expression on a subset of myofibers and macrophages. In humans, the CT carbohydrate was ectopically expressed on the sarcolemmal membrane of some BMD muscles, but not normal human or DMD muscles. These data are consistent with the notion that altered Neu5Gc and CT carbohydrate expression may modify disease severity resulting from dystrophin deficiency in dogs and humans. PMID:24505439

  7. Long-Term Warming Alters Carbohydrate Degradation Potential in Temperate Forest Soils

    PubMed Central

    Billings, Andrew F.; Blanchard, Jeff L.; Burkhardt, Daniel B.; Frey, Serita D.; Melillo, Jerry M.; Schnabel, Julia; van Diepen, Linda T. A.

    2016-01-01

    ABSTRACT As Earth's climate warms, soil carbon pools and the microbial communities that process them may change, altering the way in which carbon is recycled in soil. In this study, we used a combination of metagenomics and bacterial cultivation to evaluate the hypothesis that experimentally raising soil temperatures by 5°C for 5, 8, or 20 years increased the potential for temperate forest soil microbial communities to degrade carbohydrates. Warming decreased the proportion of carbohydrate-degrading genes in the organic horizon derived from eukaryotes and increased the fraction of genes in the mineral soil associated with Actinobacteria in all studies. Genes associated with carbohydrate degradation increased in the organic horizon after 5 years of warming but had decreased in the organic horizon after warming the soil continuously for 20 years. However, a greater proportion of the 295 bacteria from 6 phyla (10 classes, 14 orders, and 34 families) isolated from heated plots in the 20-year experiment were able to depolymerize cellulose and xylan than bacterial isolates from control soils. Together, these findings indicate that the enrichment of bacteria capable of degrading carbohydrates could be important for accelerated carbon cycling in a warmer world. IMPORTANCE The massive carbon stocks currently held in soils have been built up over millennia, and while numerous lines of evidence indicate that climate change will accelerate the processing of this carbon, it is unclear whether the genetic repertoire of the microbes responsible for this elevated activity will also change. In this study, we showed that bacteria isolated from plots subject to 20 years of 5°C of warming were more likely to depolymerize the plant polymers xylan and cellulose, but that carbohydrate degradation capacity is not uniformly enriched by warming treatment in the metagenomes of soil microbial communities. This study illustrates the utility of combining culture-dependent and culture

  8. Muscle and Liver Carbohydrates: Response to Military Task Performance by Women and Men

    DTIC Science & Technology

    2000-10-01

    effect of three different nutritional supplements upon muscle glycogen recovery. Since altering our protocol, we have made significant progress in...consecutive days of exercise) of the project (Hypothesis IV). D. Initiating an appropriate exercise protocol to study the effects of nutritional supplementation... nutritional supplementation following severe glycogen depleting exercise. 9) Initiate this final portion of the project and obtain data from a significant

  9. Regulation of skeletal muscle carbohydrate oxidation during steady-state contraction.

    PubMed

    Timmons, J A; Poucher, S M; Constantin-Teodosiu, D; Macdonald, I A; Greenhaff, P L

    1998-05-01

    Pyruvate dehydrogenase complex (PDC) activation status has been described as being central in the regulation of tissue substrate oxidation as outlined by the glucose fatty-acid cycle. In the present study we examined the effects of reduced lipolysis, with use of nicotinate, and increased PDC activation, with use of dichloroacetate (DCA), on substrate utilization during 20 min of submaximal steady-state contraction (approximately 80% of maximal O2 uptake) in canine gracilis skeletal muscle. At rest, PDC activation was unchanged by nicotinate but was approximately 2.5-fold higher in the DCA group than in the control group (P < 0.05). During contraction, PDC activation status increased to 3.5 mmol acetyl-CoA.min-1.kg-1 at 37 degrees C in the control group, remained at 4.5 mmol acetyl-CoA.min-1.kg-1 at 37 degrees C in the DCA group, but only increased to 2.2 mmol acetyl-CoA.min-1.kg-1 at 37 degrees C in the nicotinate group (P < 0.05). However, the estimated amount of carbohydrate oxidized during the 20-min contraction was similar across groups and did not follow the degree of PDC activation (81.2 +/- 22.9, 95.9 +/- 11.7, and 89.3 +/- 18.9 mmol glucosyl units/kg dry muscle for control, nicotinate, and DCA, respectively). Thus it would appear that, during steady-state contraction, PDC activation status does not determine the rate of carbohydrate oxidation in skeletal muscle.

  10. Decreased tumorigenicity correlates with expression of altered cell surface carbohydrates in Lec9 CHO cells.

    PubMed Central

    Ripka, J; Shin, S; Stanley, P

    1986-01-01

    To investigate a role for surface carbohydrates in cellular malignancy, 15 different glycosylation-defective CHO cell mutants were examined for their tumorigenic and metastatic capacities after subcutaneous injection into nude mice. Most of the glycosylation mutants displayed similar or slightly decreased tumorigenicity compared with parental CHO cells. Neither parental CHO cells nor any of the mutants were observed to metastasize. However, independent isolates of one mutant type, Lec9, showed a dramatic reduction in tumor formation. The altered carbohydrates expressed at the surface of Lec9 cells appeared to be responsible for their loss of tumorigenicity, because revertants for lectin resistance were able to form tumors, and a double mutant (Lec9.Lec1) that expressed a Lec1 glycosylation phenotype also formed tumors. Finally, Lec9 cells were able to form tumors in gamma-irradiated nude mice, suggesting that recognition by an irradiation-sensitive host cell(s) was responsible for their reduced tumorigenicity in untreated nude mice. PMID:3785164

  11. Effect of carbohydrate-protein supplementation postexercise on rat muscle glycogen synthesis and phosphorylation of proteins controlling glucose storage.

    PubMed

    Hara, Daisuke; Morrison, Paul J; Ding, Zhenping; Ivy, John L

    2011-10-01

    To examine whether addition of protein to a carbohydrate supplement enhances muscle glycogen synthesis, we compared the muscle glycogen concentrations of rats that had been depleted of their muscle glycogen stores with a 3-hour swim and immediately supplemented with a placebo (Con), carbohydrate (CHO), or carbohydrate plus protein supplement (C+P). Rats were given either 0.9 g carbohydrate per kilogram body mass for the CHO group or 0.9 g carbohydrate + 0.3 g protein per kilogram body mass for the C+P groups. Muscle samples of the red and white quadriceps were excised immediately, 30 minutes, or 90 minutes postexercise. Glycogen concentration of the C+P group was greater than that of the CHO group at 90 minutes postexercise in both red (C+P, 28.3 ± 2.6 µmol/g vs CHO, 22.4 ± 2.0 µmol/g; P < .05) and white (C+P, 24.9 ± 2.4 µmol/g vs CHO, 17.64 ± 1.5 µmol/g; P < .01) quadriceps. Protein kinase B phosphorylation was greater in the C+P-30 group (the number following treatment group abbreviation refers to time [in minutes] of euthanasia following exercise) than the sedentary control and exercised control groups in red quadriceps at 30 minutes and in white quadriceps at 90 minutes postexercise. This difference was not observed in the CHO group. Phosphorylation of glycogen synthase was significantly reduced 30 minutes postexercise and returned to baseline levels by 90 minutes postexercise in both CHO- and C+P-supplemented groups, with no difference between supplements. These results demonstrated that the addition of protein to a carbohydrate supplement will enhance the rate of muscle glycogen restoration postexercise and may involve facilitation of the glucose transport process. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients.

    PubMed

    Godard, Michael P; Whitman, Samantha A; Song, Yao-Hua; Delafontaine, Patrice

    2012-01-01

    Heart failure (HF), a debilitating disease in a growing number of adults, exerts structural and neurohormonal changes in both cardiac and skeletal muscles. However, these alterations and their affected molecular pathways remain uncharacterized. Disease progression is known to transform skeletal muscle fiber composition by unknown mechanisms. In addition, perturbation of specific hormonal pathways, including those involving skeletal muscle insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-5 (IGFB-5) appears to occur, likely affecting muscle metabolism and regeneration. We hypothesized that changes in IGF-1 and IGFB-5 mRNA levels correlate with the transformation of single-skeletal muscle fiber myosin heavy chain isoforms early in disease progression, making these molecules valuable markers of skeletal muscle changes in heart failure. To investigate these molecules during "early" events in HF patients, we obtained skeletal muscle biopsies from New York Heart Association (NYHA) Class II HF patients and controls for molecular analyses of single fibers, and we also quantified isometric strength and muscle size. There were more (P < 0.05) single muscle fibers coexpressing two or more myosin heavy chains in the HF patients (30% ± 7%) compared to the control subjects (13% ± 2%). IGF-1 and IGFBP-5 expression was fivefold and 15-fold lower in patients with in HF compared to control subjects (P < 0.05), respectively. Strikingly, there was a correlation in IGF-1 expression and muscle cross-sectional area (P < 0.05) resulting in a decrease in whole-muscle quality (P < 0.05) in the HF patients, despite no significant decrease in isometric strength or whole-muscle size. These data indicate that molecular alterations in myosin heavy chain isoforms, IGF-1, and IGFB-5 levels precede the gross morphological and functional deficits that have previously been associated with HF, and may be used as a predictor of functional outcome in patients.

  13. High-Intensity Exercise and Carbohydrate Supplementation do not Alter Plasma Visfatin

    PubMed Central

    Mellick, Paul F.; Feger, Bryan J.; Oberlin, Douglas J.; Davis, Paul G.; Wideman, Laurie

    2017-01-01

    The purpose of the study was to examine the effect of high-intensity exercise and carbohydrate supplementation (CHO) on plasma visfatin. On 2 separate days, 10 sprint-trained males (age = 26.4 ± 5.3 yr; Ht = 1.77 ± 0.03 m; Wt = 78.78 ± 9.10 kg; BF% = 13.96 ± 7.28%) completed 4, 3-min bouts of cycling at 50% mean anaerobic power, with 6 min of rest between bouts. On CHO day, subjects ingested 50g of CHO 30 min before exercise. On control day, subjects ingested a sugar-free drink (CON) 30 min before exercise. Blood was drawn before supplementation, 15 min before exercise, before and after each exercise bout, and 15 and 30 min post exercise. Visfatin, glucose, and insulin were determined. Truncal fat was assessed by dual energy x-ray. Visfatin was not significantly different between treatments (CHO vs CON) at any time point (p = 0.163), and was not significantly altered by exercise (p = 0.692). Insulin [25.65 vs 8.35 mU/l, CHO vs CON, respectively] and glucose [138.57 vs 98.10 mg/dl, CHO vs CON, respectively] were significantly elevated after CHO ingestion and remained elevated throughout the first half of exercise. Baseline visfatin was significantly correlated with truncal fat (r2 = 0.7782, p < 0.05). Visfatin was correlated to truncal fat in sprint-trained males, but was not altered by exercise or CHO supplementation. Key points Plasma visfatin was not affected by exercise or carbohydrate supplementation. Plasma visfatin was significantly correlated to abdominal fat. Plasma visfatin did not follow a similar pattern to blood glucose or plasma insulin as has been shown in previous studies. PMID:28344453

  14. Altered cross-bridge properties in skeletal muscle dystrophies.

    PubMed

    Guellich, Aziz; Negroni, Elisa; Decostre, Valérie; Demoule, Alexandre; Coirault, Catherine

    2014-01-01

    Force and motion generated by skeletal muscle ultimately depends on the cyclical interaction of actin with myosin. This mechanical process is regulated by intracellular Ca(2+) through the thin filament-associated regulatory proteins i.e.; troponins and tropomyosin. Muscular dystrophies are a group of heterogeneous genetic affections characterized by progressive degeneration and weakness of the skeletal muscle as a consequence of loss of muscle tissue which directly reduces the number of potential myosin cross-bridges involved in force production. Mutations in genes responsible for skeletal muscle dystrophies (MDs) have been shown to modify the function of contractile proteins and cross-bridge interactions. Altered gene expression or RNA splicing or post-translational modifications of contractile proteins such as those related to oxidative stress, may affect cross-bridge function by modifying key proteins of the excitation-contraction coupling. Micro-architectural change in myofilament is another mechanism of altered cross-bridge performance. In this review, we provide an overview about changes in cross-bridge performance in skeletal MDs and discuss their ultimate impacts on striated muscle function.

  15. Altered cross-bridge properties in skeletal muscle dystrophies

    PubMed Central

    Guellich, Aziz; Negroni, Elisa; Decostre, Valérie; Demoule, Alexandre; Coirault, Catherine

    2014-01-01

    Force and motion generated by skeletal muscle ultimately depends on the cyclical interaction of actin with myosin. This mechanical process is regulated by intracellular Ca2+ through the thin filament-associated regulatory proteins i.e.; troponins and tropomyosin. Muscular dystrophies are a group of heterogeneous genetic affections characterized by progressive degeneration and weakness of the skeletal muscle as a consequence of loss of muscle tissue which directly reduces the number of potential myosin cross-bridges involved in force production. Mutations in genes responsible for skeletal muscle dystrophies (MDs) have been shown to modify the function of contractile proteins and cross-bridge interactions. Altered gene expression or RNA splicing or post-translational modifications of contractile proteins such as those related to oxidative stress, may affect cross-bridge function by modifying key proteins of the excitation-contraction coupling. Micro-architectural change in myofilament is another mechanism of altered cross-bridge performance. In this review, we provide an overview about changes in cross-bridge performance in skeletal MDs and discuss their ultimate impacts on striated muscle function. PMID:25352808

  16. Castration alters protein balance after high-frequency muscle contraction.

    PubMed

    Steiner, Jennifer L; Fukuda, David H; Rossetti, Michael L; Hoffman, Jay R; Gordon, Bradley S

    2017-02-01

    Resistance exercise increases muscle mass by shifting protein balance in favor of protein accretion. Androgens independently alter protein balance, but it is unknown whether androgens alter this measure after resistance exercise. To answer this, male mice were subjected to sham or castration surgery 7-8 wk before undergoing a bout of unilateral, high-frequency, electrically induced muscle contractions in the fasted or refed state. Puromycin was injected 30 min before euthanasia to measure protein synthesis. The tibialis anterior was analyzed 4 h postcontraction. In fasted mice, neither basal nor stimulated rates of protein synthesis were affected by castration despite lower phosphorylation of mechanistic target of rapamycin in complex 1 (mTORC1) substrates [p70S6K1 (Thr389) and 4E-BP1 (Ser65)]. Markers of autophagy (LC3 II/I ratio and p62 protein content) were elevated by castration, and these measures remained elevated above sham values after contractions. Furthermore, in fasted mice, the protein content of Regulated in Development and DNA Damage 1 (REDD1) was correlated with LC3 II/I in noncontracted muscle, whereas phosphorylation of uncoordinated like kinase 1 (ULK1) (Ser757) was correlated with LC3 II/I in the contracted muscle. When mice were refed before contractions, protein synthesis and mTORC1 signaling were not affected by castration in either the noncontracted or contracted muscle. Conversely, markers of autophagy remained elevated in the muscles of refed, castrated mice even after contractions. These data suggest the castration-mediated elevation in baseline autophagy reduces the absolute positive shift in protein balance after muscle contractions in the refed or fasted states.

  17. Skeletal muscle fat and carbohydrate metabolism during recovery from glycogen-depleting exercise in humans

    PubMed Central

    Kimber, Nicholas E; Heigenhauser, George J F; Spriet, Lawrence L; Dyck, David J

    2003-01-01

    The primary aim of the present study was to determine whether intramuscular triacylglycerol (IMTG) utilization contributed significantly to the increase in lipid oxidation during recovery from exercise, as determined from the muscle biopsy technique. In addition, we also examined the regulation of pyruvate dehydrogenase (PDHa) and changes in muscle acetyl units during an 18 h recovery period after glycogen-depleting exercise. Eight endurance-trained males completed an exhaustive bout of exercise (∼90 min) on a cycle ergometer followed by ingestion of carbohydrate (CHO)-rich meals (64–70 % of energy from carbohydrate) at 1, 4 and 7 h of recovery. Duplicate muscle biopsies were obtained at exhaustion, and 3, 6 and 18 h of recovery. Despite the large intake of CHO during recovery (491 ± 28 g or 6.8 ± 0.3 g kg−1), respiratory exchange ratio values of 0.77 to 0.84 indicated a greater reliance on lipid as an oxidative fuel. However, there was no net IMTG utilization during recovery. IMTG content at exhaustion was 23.5 ± 3.5 mmol (kg dry wt)−1, and remained constant at 24.6 ± 2.6, 25.7 ± 2.8 and 28.4 ± 3.0 mmol (kg dry wt)−1 after 3, 6 and 18 h of recovery. Muscle glycogen increased significantly from 37 ± 11 mmol (kg dry wt)−1 at exhaustion, to 165 ± 13, 250 ± 18, and 424 ± 22 mmol (kg dry wt)−1 at 3, 6 and 18 h of recovery, respectively. PDHa was reduced at 6 and 18 h when compared to exhaustion, but did not change during the recovery period. Acetyl-CoA, acetylcarnitine and pyruvate contents declined significantly after 3 h of recovery compared to exhaustion, and thereafter remained unchanged. We conclude that IMTG has a negligible role in contributing to the enhanced fat oxidation during recovery from exhaustive exercise. Despite the elevation of glucose and insulin following high-CHO meals during recovery, CHO oxidation and PDH activation were decreased, supporting the hypothesis that glycogen resynthesis is of high metabolic priority. Plasma

  18. Altered Ca2+ sparks in aging skeletal and cardiac muscle

    PubMed Central

    Weisleder, Noah; Ma, Jianjie

    2008-01-01

    Ca2+ sparks are the fundamental units that comprise Ca2+-induced Ca2+ release (CICR) in striated muscle cells. In cardiac muscle, spontaneous Ca2+ sparks underlie the rhythmic CICR activity during heart contraction. In skeletal muscle, Ca2+ sparks remain quiescent during the resting state and are activated in a plastic fashion to accommodate various levels of stress. With aging, the plastic Ca2+ spark signal becomes static in skeletal muscle, whereas loss of CICR control leads to leaky Ca2+ spark activity in aged cardiomyocytes. Ca2+ spark responses reflect the integrated function of the intracellular Ca2+ regulatory machinery centered around the triad or dyad junctional complexes of striated muscles, which harbor the principal molecular players of excitation-contraction coupling. This review highlights the contribution of age-related modification of the Ca2+ release machinery and the effect of membrane structure and membrane cross-talk on the altered Ca2+ spark signaling during aging of striated muscles. PMID:18272434

  19. Effects of Taurine Administration on Carbohydrate Metabolism in Skeletal Muscle during the Post-Exercise Phase.

    PubMed

    Takahashi, Yumiko; Tamura, Yuki; Matsunaga, Yutaka; Kitaoka, Yu; Terada, Shin; Hatta, Hideo

    2016-01-01

    We previously reported that taurine (2-aminoethanesulfonic acid; dose: 0.5 mg/g body weight) administration after treadmill running at 25 m/min for 90 min increased the glycogen concentration in the skeletal muscle of ICR mice at 120 min after the exercise (Takahashi et al. 2014). In the current study, we further investigated the effects of taurine administration on glycogen repletion and carbohydrate metabolism in the tibialis anterior muscle after endurance exercise. The metabolomic profiles of the tibialis anterior muscle at 120 min after the exercise were analyzed by a capillary electrophoresis-time-of-flight mass spectrometry (n=6). Fructose-1,6-bisphosphate (F1,6P), a glycogenolytic/glycolytic intermediate produced by phosphofructokinase, was significantly lower in the taurine-treated group than that in the control group (p<0.01). Dihydroxyacetonephosphate (DHAP), a downstream product of F1,6P was lower (p=0.05) and glycerol 3-phosphate, a downstream product of F1,6P and DHAP, tended to be lower (p=0.09) in the taurine-treated group than in the controls. At that time, phosphorylated Ser(293) on the E1α subunit of pyruvate dehydrogenase (PDH) tended to be higher in the taurine-treated mice than in the controls (p=0.09, n=5). There was a positive correlation between phosphorylation of the PDH E1α subunit at Ser(293) and glycogen concentration (r=0.73, p<0.05). Our results showed that the enhanced glycogen repletion in skeletal muscle by taurine treatment during the post-exercise phase was accompanied by the lower levels of glycogenolytic/glycolytic intermediates.

  20. Selenium Protects Retinal Cells from Cisplatin-Induced Alterations in Carbohydrate Residues

    PubMed Central

    Akşit, Dilek; Yazıcı, Alper; Akşit, Hasan; Sarı, Esin S.; Yay, Arzu; Yıldız, Onur; Kılıç, Adil; Ermiş, Sıtkı S.; Seyrek, Kamil

    2016-01-01

    Background: Investigate alterations in the expression and localization of carbohydrate units in rat retinal cells exposed to cisplatin toxicity. Aims: The aim of the study was to evaluate putative protective effects of selenium on retinal cells subjected to cisplatin. Study Design: Animal experiment. Methods: Eighteen healthy Wistar rats were divided into three equal groups: 1. Control, 2. Cisplatin and 3. Cisplatin+selenium groups. After anesthesia, the right eye of each rat was enucleated. Results: Histochemically, retinal cells of control groups reacted with α-2,3-bound sialic acid-specific Maackia amurensis lectin (MAA) strongly, while cisplatin reduced the staining intensity for MAA. However, selenium administration alleviated the reducing effect of cisplatin on the binding sites for MAA in retinal cells. The staining intensity for N-acetylgalactosamine (GalNAc residues) specific Griffonia simplicifolia-1 (GSL–1) was relatively slight in control animals and cisplatin reduced this slight staining for GSL-1 further. Selenium administration mitigated the reducing effect of cisplatin on the binding sites for GSL-1. A diffuse staining for N-acetylglucosamine (GlcNAc) specific wheat germ agglutinin (WGA) was observed throughout the retina of the control animals. In particular, cells localized in the inner plexiform and photoreceptor layers are reacted strongly with WGA. Compared to the control animals, binding sites for WGA in the retina of rats given cisplatin were remarkably decreased. However, the retinal cells of rats given selenium reacted strongly with WGA. Conclusion: Cisplatin reduces α-2,3-bound sialic acid, GlcNAc and GalNAc residues in certain retinal cells. However, selenium alleviates the reducing effect of cisplatin on carbohydrate residues in retinal cells. PMID:27606141

  1. Carbohydrate supplementation and alterations in neutrophils, and plasma cortisol and myoglobin concentration after intense exercise.

    PubMed

    Peake, Jonathan; Wilson, Gary; Mackinnon, Laurel; Coombes, Jeff S

    2005-03-01

    The present study examined the effect of carbohydrate supplementation on changes in neutrophil counts, and the plasma concentrations of cortisol and myoglobin after intense exercise. Eight well-trained male runners ran on a treadmill for 1 h at 85% maximal oxygen uptake on two separate occasions. In a double-blind cross-over design, subjects consumed either 750 ml of a 10% carbohydrate (CHO) drink or a placebo drink on each occasion. The order of the trials was counter-balanced. Blood was drawn immediately before and after exercise, and 1 h after exercise. Immediately after exercise, neutrophil counts (CHO, 49%; placebo, 65%; P<0.05), plasma concentrations of glucose (CHO, 43%; P<0.05), lactate (CHO, 130%; placebo, 130%; P<0.01), cortisol (CHO, 100%; placebo, 161%; P<0.01), myoglobin (CHO, 194%; placebo, 342%; P<0.01) all increased significantly. One hour post-exercise, plasma myoglobin concentration (CHO, 331%; placebo, 482%; P<0.01) and neutrophil count (CHO, 151%; placebo, 230% P<0.01) both increased further above baseline. CHO significantly attenuated plasma myoglobin concentration and the neutrophil count after exercise (P<0.01), but did not affect plasma cortisol concentration. The effects of CHO on plasma myoglobin concentration may be due to alterations in cytokine synthesis, insulin responses or myoglobin clearance rates from the bloodstream during exercise. Plasma cortisol responses to CHO during exercise may depend on the intensity of exercise, or the amount of CHO consumed. Lastly, cortisol appears to play a minor role in the mobilisation of neutrophils after intense exercise.

  2. Influences of carbohydrate plus amino acid supplementation on differing exercise intensity adaptations in older persons: skeletal muscle and endocrine responses.

    PubMed

    Onambélé-Pearson, Gladys Leopoldine; Breen, Leigh; Stewart, Claire E

    2010-06-01

    Losses in physiological function in healthy ageing occur partly as a consequence of reduced protein intake and partly as a consequence of less than 30-min/day of moderate to vigorous physical activity. The current study aimed to compare the effects of two different intensities of resistance training in healthy older adults, whose habitual dietary intake was supplemented with carbohydrate and amino acid preparations. We hypothesised that although intensive exercise with appropriate carbohydrate and amino acid supplementation would result in the most profound impact on in vivo markers of healthy physiologic and endocrine functions in previously sedentary older individuals, the effectiveness of the less intense exercise prescription with supplementation would also result in beneficial adaptations over and above findings of previous studies on low intensity exercise alone. Twenty-nine older adults (out of 32) completed the study after being randomly assigned to low (SUP_LowR, i.e., approximately 40% 1RM; n = 16) versus high resistance training (SUP_HighR, i.e., approximately 80% 1RM; n = 13) for 12 weeks. A carbohydrate supplement was ingested immediately before and during every exercise session and an amino acid cocktail was ingested post-exercise. Neither intervention significantly impacted upon body composition assessed using: Body mass index, waist/hip ratio and bioelectric impedance. Muscle strength increased similarly in the two groups with the SUP_HighR protocol showing 46 +/- 8%, 10.8 +/- 4.4% and 26.9 +/- 4.9% (P < 0.01) improvements in 1-RM strength, unilateral and bilateral knee extension torque, respectively, compared with 39 +/- 2%, 9.4 +/- 3.7% and 29.5 +/- 8.2% (P < 0.01) increments in the same measures in the SUP_LowR group. Lean muscle thickness however, showed a greater benefit of the SUP_LowR protocol (8.7 +/- 3.9% increase, P < 0.05) compared with the SUP_HighR protocol, which elicited no significant change. In terms of functional abilities, only

  3. Alterations in carbohydrate metabolism and its regulation in PPARalpha null mouse hearts.

    PubMed

    Gélinas, Roselle; Labarthe, François; Bouchard, Bertrand; Mc Duff, Janie; Charron, Guy; Young, Martin E; Des Rosiers, Christine

    2008-04-01

    Although a shift from fatty acids (FAs) to carbohydrates (CHOs) is considered beneficial for the diseased heart, it is unclear why subjects with FA beta-oxidation defects are prone to cardiac decompensation under stress conditions. The present study investigated potential alterations in the myocardial utilization of CHOs for energy production and anaplerosis in 12-wk-old peroxisome proliferator-activating receptor-alpha (PPARalpha) null mice (a model of FA beta-oxidation defects). Carbon-13 methodology was used to assess substrate flux through energy-yielding pathways in hearts perfused ex vivo at two workloads with a physiological substrate mixture mimicking the fed state, and real-time RT-quantitative polymerase chain reaction was used to document the expression of selected metabolic genes. When compared with that from control C57BL/6 mice, isolated working hearts from PPARalpha null mice displayed an impaired capacity to withstand a rise in preload (mimicking an increased venous return as it occurs during exercise) as reflected by a 20% decline in the aortic flow rate. At the metabolic level, beyond the expected shift from FA (5-fold down) to CHO (1.5-fold up; P < 0.001) at both preloads, PPARalpha null hearts also displayed 1) a significantly greater contribution of exogenous lactate and glucose and/or glycogen (2-fold up) to endogenous pyruvate formation, whereas that of exogenous pyruvate remained unchanged and 2) marginal alterations in citric acid cycle-related parameters. The lactate production rate was the only measured parameter that was affected differently by preloads in control and PPARalpha null mouse hearts, suggesting a restricted reserve for the latter hearts to enhance glycolysis when the energy demand is increased. Alterations in the expression of some glycolysis-related genes suggest potential mechanisms involved in this defective CHO metabolism. Collectively, our data highlight the importance of metabolic alterations in CHO metabolism

  4. Altered muscle force and stiffness of skeletal muscles in alpha-sarcoglycan-deficient mice.

    PubMed

    Patel, Nisha D; Jannapureddy, Suneal R; Hwang, Willy; Chaudhry, Imran; Boriek, Aladin M

    2003-04-01

    Alpha-sarcoglycan (ASG) is a transmembrane protein of the dystrophin-associated complex, and absence of ASG causes limb-girdle muscular dystrophy. We hypothesize that disruption of the sarcoglycan complex may alter muscle extensibility and disrupt the coupling between passive transverse and axial contractile elements in the diaphragm. We determined the length-tension relationships of the diaphragm of young ASG-deficient mice and their controls during uniaxial and biaxial loading. We also determined the isometric contractile properties of the diaphragm muscles from mutant and normal mice in the absence and presence of passive transverse stress. We found that the diaphragm muscles of the null mutants for the protein ASG show 1) significant decrease in muscle extensibility in the directions of the muscle fibers and transverse to fibers, 2) significant reductions in force-generating capacity, and 3) significant reductions in coupling between longitudinal and transverse properties. Thus these findings suggest that the sarcoglycan complex serves a mechanical function in the diaphragm by contributing to muscle passive stiffness and to the modulation of the contractile properties of the muscle.

  5. Arsenic exposure to killifish during embryogenesis alters muscle development.

    PubMed

    Gaworecki, Kristen M; Chapman, Robert W; Neely, Marion G; D'Amico, Angela R; Bain, Lisa J

    2012-02-01

    Epidemiological studies have correlated arsenic exposure in drinking water with adverse developmental outcomes such as stillbirths, spontaneous abortions, neonatal mortality, low birth weight, delays in the use of musculature, and altered locomotor activity. Killifish (Fundulus heteroclitus) were used as a model to help to determine the mechanisms by which arsenic could impact development. Killifish embryos were exposed to three different sodium arsenite concentrations and were collected at 32 h post-fertilization (hpf), 42 hpf, 168 hpf, or < 24 h post-hatch. A killifish oligo microarray was developed and used to examine gene expression changes between control and 25-ppm arsenic-exposed hatchlings. With artificial neural network analysis of the transcriptomic data, accurate prediction of each group (control vs. arsenic-exposed embryos) was obtained using a small subset of only 332 genes. The genes differentially expressed include those involved in cell cycle, development, ubiquitination, and the musculature. Several of the genes involved in cell cycle regulation and muscle formation, such as fetuin B, cyclin D-binding protein 1, and CapZ, were differentially expressed in the embryos in a time- and dose-dependent manner. Examining muscle structure in the hatchlings showed that arsenic exposure during embryogenesis significantly reduces the average muscle fiber size, which is coupled with a significant 2.1- and 1.6-fold upregulation of skeletal myosin light and heavy chains, respectively. These findings collectively indicate that arsenic exposure during embryogenesis can initiate molecular changes that appear to lead to aberrant muscle formation.

  6. High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine.

    PubMed

    Pedersen, David J; Lessard, Sarah J; Coffey, Vernon G; Churchley, Emmanuel G; Wootton, Andrew M; Ng, They; Watt, Matthew J; Hawley, John A

    2008-07-01

    We determined the effect of coingestion of caffeine (Caff) with carbohydrate (CHO) on rates of muscle glycogen resynthesis during recovery from exhaustive exercise in seven trained subjects who completed two experimental trials in a randomized, double-blind crossover design. The evening before an experiment subjects performed intermittent exhaustive cycling and then consumed a low-CHO meal. The next morning subjects rode until volitional fatigue. On completion of this ride subjects consumed either CHO [4 g/kg body mass (BM)] or the same amount of CHO + Caff (8 mg/kg BM) during 4 h of passive recovery. Muscle biopsies and blood samples were taken at regular intervals throughout recovery. Muscle glycogen levels were similar at exhaustion [ approximately 75 mmol/kg dry wt (dw)] and increased by a similar amount ( approximately 80%) after 1 h of recovery (133 +/- 37.8 vs. 149 +/- 48 mmol/kg dw for CHO and Caff, respectively). After 4 h of recovery Caff resulted in higher glycogen accumulation (313 +/- 69 vs. 234 +/- 50 mmol/kg dw, P < 0.001). Accordingly, the overall rate of resynthesis for the 4-h recovery period was 66% higher in Caff compared with CHO (57.7 +/- 18.5 vs. 38.0 +/- 7.7 mmol x kg dw(-1) x h(-1), P < 0.05). After 1 h of recovery plasma Caff levels had increased to 31 +/- 11 microM (P < 0.001) and at the end of the recovery reached 77 +/- 11 microM (P < 0.001) with Caff. Phosphorylation of CaMK(Thr286) was similar after exercise and after 1 h of recovery, but after 4 h CaMK(Thr286) phosphorylation was higher in Caff than CHO (P < 0.05). Phosphorylation of AMP-activated protein kinase (AMPK)(Thr172) and Akt(Ser473) was similar for both treatments at all time points. We provide the first evidence that in trained subjects coingestion of large amounts of Caff (8 mg/kg BM) with CHO has an additive effect on rates of postexercise muscle glycogen accumulation compared with consumption of CHO alone.

  7. Effects of Short-Term Carbohydrate Restrictive and Conventional Hypoenergetic Diets and Resistance Training on Strength Gains and Muscle Thickness

    PubMed Central

    Meirelles, Claudia M.; Gomes, Paulo S.C.

    2016-01-01

    Hypoenergetic diets and resistance training (RT) have been suggested to be important components of weight loss strategy programs; however, there is little evidence as to the chronic effects of different macronutrient compositions on strength performance and muscle mass with RT. The purpose of this study was to compare the effects of carbohydrate restrictive (CRD) and conventional (CONV) diets combined with RT on strength performance and muscle thicknesses in overweight and obese participants already involved in RT programs. Twenty-one volunteers engaged in an eight-week progressive RT program three times per week were assigned to a CRD (< 30 g carbohydrate; n = 12; 30.7 ± 3.9 km·m-2) or a CONV (30% energy deficit; 55%, 15% and 30% energy from carbohydrate, protein and fat, respectively; n=9; 27.7±2.5 km·m-2). Method: At baseline and week 8, the participants underwent body composition assessment by anthropometry, measurement of muscle thickness by ultrasound, and three strength tests using isotonic equipment. Both groups had similar reductions in body mass and fat mass as well as maintenance of fat-free mass. Muscle strength increased 14 ± 6% in the CRD group (p = 0.005) and 19 ± 9% in the CONV group (p = 0.028), with no significant differences between the groups. No significant differences were detected in muscle thicknesses within or between the groups. In conclusion, hypoenergetic diets combined with RT led to significant increases in muscle strength and were capable of maintaining muscle thicknesses in the upper and lower limbs of overweight and obese participants, regardless of the carbohydrate content of the diets. Key points The study deals with the effects of carbohydrate restrictive diet associated to a typical resistance training program, in obese and overweight individuals. The study presents greater external validity, since it was devised in an actual fitness center setting with physically active participants enrolled in exercise programs in three

  8. Skeletal Muscle myomiR Are Differentially Expressed by Endurance Exercise Mode and Combined Essential Amino Acid and Carbohydrate Supplementation

    PubMed Central

    Margolis, Lee M.; McClung, Holly L.; Murphy, Nancy E.; Carrigan, Christopher T.; Pasiakos, Stefan M.

    2017-01-01

    Skeletal muscle microRNAs (myomiR) expression is modulated by exercise, however, the influence of endurance exercise mode, combined with essential amino acid and carbohydrate (EAA+CHO) supplementation are not well defined. This study determined the effects of weighted versus non-weighted endurance exercise, with or without EAA+CHO ingestion on myomiR expression and their association with muscle protein synthesis (MPS). Twenty five adults performed 90 min of metabolically-matched (2.2 VO2 L·m−1) load carriage (LC; performed on a treadmill wearing a vest equal to 30% of individual body mass) or cycle ergometry (CE) exercise, during which EAA+CHO (10 g EAA and 46 g CHO) or non-nutritive control (CON) drinks were consumed. Expression of myomiR (RT-qPCR) were determined at rest (PRE), immediately post-exercise (POST), and 3 h into recovery (REC). Muscle protein synthesis (2H5-phenylalanine) was measured during exercise and recovery. Relative to PRE, POST, and REC expression of miR-1-3p, miR-206, miR-208a-5, and miR-499 was lower (P < 0.05) for LC compared to CE, regardless of dietary treatment. Independent of exercise mode, miR-1-3p and miR-208a-5p expression were lower (P < 0.05) after ingesting EAA+CHO compared to CON. Expression of miR-206 was highest for CE-CON than any other treatment (exercise-by-drink, P < 0.05). Common targets of differing myomiR were identified as markers within mTORC1 signaling, and miR-206 and miR-499 were inversely associated with MPS rates immediately post-exercise. These findings suggest the alterations in myomiR expression between exercise mode and EAA+CHO intake may in part be due to differing MPS modulation immediately post-exercise. PMID:28386239

  9. Timing influence of carbohydrate-protein ingestion on muscle soreness and next-day running performance.

    PubMed

    Greer, Beau Kjerulf; Price, Anna; Jones, Brett

    2014-06-01

    The present study investigates timing effects of a carbohydrate-protein (CHO-PROT) beverage on indicators of muscle damage and next day running performance. Nine trained subjects completed three trials of a 30 min downhill run, followed by a 1.5 mile treadmill running time trial 24 hr later in a blinded, crossover design. Either a CHO-PROT or noncaloric placebo beverage was given 30 and 5 min prior to, at the 15 min mark during, immediately after, and 30 min after the downhill running protocol. In the first treatment (T1), a total of 360 kilocalories were given 30 and 5 min prior to downhill running, as well as at the 15 min mark, with placebos used at other time points. In the second treatment (T2), an isocaloric amount was given but only immediately after and 30 min after downhill running, with placebos used at other time points. In the placebo treatment, a placebo was given at all time points. There were no significant differences in the 1.5 mile time trial or soreness between trials (p > .05). Regardless of timing, the ingestion of a CHO-PROT beverage had no effect on next day running performance or muscular soreness versus a placebo.

  10. The ingestion of combined carbohydrates does not alter metabolic responses or performance capacity during soccer-specific exercise in the heat compared to ingestion of a single carbohydrate.

    PubMed

    Clarke, N D; Campbell, I T; Drust, B; Evans, L; Reilly, T; Maclaren, D P M

    2012-01-01

    This study was designed to investigate the effect of ingesting a glucose plus fructose solution on the metabolic responses to soccer-specific exercise in the heat and the impact on subsequent exercise capacity. Eleven male soccer players performed a 90 min soccer-specific protocol on three occasions. Either 3 ml · kg(-1) body mass of a solution containing glucose (1 g · min(-1) glucose) (GLU), or glucose (0.66 g · min(-1)) plus fructose (0.33 g · min(-1)) (MIX) or placebo (PLA) was consumed every 15 minutes. Respiratory measures were undertaken at 15-min intervals, blood samples were drawn at rest, half-time and on completion of the protocol, and muscle glycogen concentration was assessed pre- and post-exercise. Following the soccer-specific protocol the Cunningham and Faulkner test was performed. No significant differences in post-exercise muscle glycogen concentration (PLA, 62.99 ± 8.39 mmol · kg wet weight(-1); GLU 68.62 ± 2.70; mmol · kg wet weight(-1) and MIX 76.63 ± 6.92 mmol · kg wet weight(-1)) or exercise capacity (PLA, 73.62 ± 8.61 s; GLU, 77.11 ± 7.17 s; MIX, 83.04 ± 9.65 s) were observed between treatments (P > 0.05). However, total carbohydrate oxidation was significantly increased during MIX compared with PLA (P < 0.05). These results suggest that when ingested in moderate amounts, the type of carbohydrate does not influence metabolism during soccer-specific intermittent exercise or affect performance capacity after exercise in the heat.

  11. Influence of in ovo injection of glutamine and carbohydrates on digestive organs and pectoralis muscle mass in the duck.

    PubMed

    Chen, W; Wang, R; Wan, H F; Xiong, X L; Peng, P; Peng, J

    2009-07-01

    1. We hypothesise that administration of available glutamine and carbohydrates by in ovo injection may provide energy for small intestine and duck embryo activity, in turn alleviating energy lack, sparing the pectoralis muscle protein and increasing breast muscle mass. To test this hypothesis, 220 duck eggs at 21 d of incubation were chosen and assigned to two treatments. At 23 d of incubation, glutamine, digestible sucrose and maltose were injected into the amniotic fluid in the treatment group. 2. In ovo injection of glutamine and carbohydrates improved small intestine development, as reflected in the increase in weight and sucrase activity, though gizzard, proventriculus and liver weight were not affected by the in ovo injection. 3. Compared with control, pectoralis weight in treatment ducks was increased by 24% at 25 d of incubation and 15% at hatch and this advantage was sustained until 7 d posthatch. In ovo injection improved duck weight gain in the early days posthatch. 4. The results of the present study suggest that in ovo injection of glutamine and carbohydrates improves small intestine development and pectoralis mass, which is probably due to sparing of breast muscle protein.

  12. The effects of adding leucine to pre and postexercise carbohydrate beverages on acute muscle recovery from resistance training.

    PubMed

    Stock, Matt S; Young, John C; Golding, Lawrence A; Kruskall, Laura J; Tandy, Richard D; Conway-Klaassen, Janice M; Beck, Travis W

    2010-08-01

    The present study examined the effects of adding leucine to pre and postexercise carbohydrate beverages on selected markers of muscle damage, delayed-onset muscle soreness (DOMS), and squat performance for up to 72 hours after lower-body resistance training. Seventeen resistance trained men (mean +/- SD age 22.9 +/- 2.9 years) and 3 resistance trained women (mean +/- SD age 21.6 +/- 2.6 years) performed 6 sets of squats to fatigue using 75% of the 1 repetition maximum. Each subject consumed a carbohydrate beverage 30 minutes before and immediately after exercise with or without the addition of 22.5 mgxkg (45 mgxkg total) of leucine in a randomized, double-blind fashion. Serum creatine kinase (CK), lactate dehydrogenase (LDH), and DOMS were analyzed immediately before (TIME1), 24 (TIME2), 48 (TIME3), and 72 (TIME4) hours after exercise. The subjects repeated the squat protocol at TIME4 to test recovery. No differences were observed between groups for squat performance, defined as the total number of repetitions performed during 6 sets of squats, for both TIME1 and TIME4. The addition of leucine did not significantly decrease CK and LDH activity or DOMS. These results suggested that adding leucine to carbohydrate beverages did not affect acute muscle recovery and squat performance during both initial testing and during a subsequent exercise bout 72 hours later in resistance trained subjects.

  13. Protein-carbohydrate supplements improve muscle protein balance in muscular dystrophy patients after endurance exercise: a placebo-controlled crossover study.

    PubMed

    Andersen, Grete; Ørngreen, Mette C; Preisler, Nicolai; Jeppesen, Tina D; Krag, Thomas O; Hauerslev, Simon; van Hall, Gerrit; Vissing, John

    2015-01-15

    In healthy individuals, postexercise protein supplementation increases muscle protein anabolism. In patients with muscular dystrophies, aerobic exercise improves muscle function, but the effect of exercise on muscle protein balance is unknown. Therefore, we investigated 1) muscle protein balance before, during, and after exercise and 2) the effect of postexercise protein-carbohydrate supplementation on muscle protein balance in patients with muscular dystrophies. In 17 patients [7 women and 10 men, aged 33 ± 11 yr (18-52), body mass index: 22 ± 3 kg/m(2) (16-26)] and 8 healthy matched controls [3 women and 5 men, age 33 ± 13 years (19-54), body mass index: 23 ± 3 kg/m(2) (19-27)], muscle protein synthesis, breakdown, and fractional synthesis rates (FSR) were measured across the leg using tracer dilution methodology on two occasions, with and without oral postexercise protein-carbohydrate supplementation. In patients, muscle protein breakdown increased in the recovery period (11 ± 1 μmol phenylalanine/min) vs. rest (8 ± 1 μmol phenylalanine/min, P = 0.02), enhancing net muscle protein loss. In contrast, postexercise protein-carbohydrate supplementation reduced protein breakdown, abolished net muscle protein loss, and increased the muscle FSR in patients (0.04 to 0.06%/h; P = 0.03). In conclusion, postexercise protein-carbohydrate supplementation reduces skeletal mixed-muscle protein breakdown, enhances FSR, resulting in a reduced net muscle loss in patients with muscular dystrophies. The findings suggest that postexercise protein-carbohydrate supplementation could be an important add-on to exercise training therapy in muscular dystrophies, and long-term studies of postexercise protein-carbohydrate supplementation are warranted in these conditions. Copyright © 2015 the American Physiological Society.

  14. Altering fatty acid availability does not impair prolonged, continuous running to fatigue: evidence for carbohydrate dependence.

    PubMed

    Leckey, Jill J; Burke, Louise M; Morton, James P; Hawley, John A

    2016-01-15

    We determined the effect of suppressing lipolysis via administration of nicotinic acid (NA) on fuel substrate selection and half-marathon running capacity. In a single-blinded, Latin square design, 12 competitive runners completed four trials involving treadmill running until volitional fatigue at a pace based on 95% of personal best half-marathon time. Trials were completed in a fed or overnight fasted state: 1) carbohydrate (CHO) ingestion before (2 g CHO·kg(-1)·body mass(-1)) and during (44 g/h) [CFED]; 2) CFED plus NA ingestion [CFED-NA]; 3) fasted with placebo ingestion during [FAST]; and 4) FAST plus NA ingestion [FAST-NA]. There was no difference in running distance (CFED, 21.53 ± 1.07; CFED-NA, 21.29 ± 1.69; FAST, 20.60 ± 2.09; FAST-NA, 20.11 ± 1.71 km) or time to fatigue between the four trials. Concentrations of plasma free fatty acids (FFA) and glycerol were suppressed following NA ingestion irrespective of preexercise nutritional intake but were higher throughout exercise in FAST compared with all other trials (P < 0.05). Rates of whole-body CHO oxidation were unaffected by NA ingestion in the CFED and FAST trials, but were lower in the FAST trial compared with the CFED-NA trial (P < 0.05). CHO was the primary substrate for exercise in all conditions, contributing 83-91% to total energy expenditure with only a small contribution from fat-based fuels. Blunting the exercise-induced increase in FFA via NA ingestion did not impair intense running capacity lasting ∼85 min, nor did it alter patterns of substrate oxidation in competitive athletes. Although there was a small but obligatory use of fat-based fuels, the oxidation of CHO-based fuels predominates during half-marathon running.

  15. Alterations in Hepatic Glucose and Energy Metabolism as a Result of Calorie and Carbohydrate Restriction

    PubMed Central

    Browning, Jeffrey D.; Weis, Brian; Davis, Jeannie; Satapati, Santhosh; Merritt, Matthew; Malloy, Craig R.; Burgess, Shawn C.

    2009-01-01

    Carbohydrate-restriction is a common weight-loss approach that modifies hepatic metabolism by increasing gluconeogenesis and ketosis. Because little is known regarding the effect of carbohydrate-restriction on the origin of gluconeogenic precursors (gluconeogenesis from glycerol (GNGglycerol) and lactate/amino acids (GNGPEP)) or its consequence to hepatic energy homeostasis, we studied these parameters in a group of overweight/obese subjects undergoing weight-loss via dietary restriction. We used 2H and 13C tracers and nuclear magnetic resonance spectroscopy to measure the sources of hepatic glucose and TCA cycle flux in weight-stable subjects(n=7) and subjects following carbohydrate-(n=7) or calorie-restriction(n=7). The majority of hepatic glucose production in carbohydrate-restricted subjects came from GNGPEP. The contribution of glycerol to gluconeogenesis was similar in all groups despite evidence of increased fat oxidation in carbohydrate-restricted subjects. A strong correlation between TCA cycle flux and GNGPEP was found, though the reliance on TCA cycle energy production for gluconeogenesis was attenuated in subjects undergoing carbohydrate restriction. Together, these data imply that the TCA cycle is the energetic patron of gluconeogenesis. However, the relationship between these two pathways is modified by carbohydrate restriction, suggesting an increased reliance of the hepatocyte on energy generated outside of the TCA cycle when GNGPEP is maximal. In conclusion, carbohydrate-restriction modifies hepatic gluconeogenesis by increasing reliance on substrates like lactate or amino acids but not glycerol. This modification is associated with a reorganization of hepatic energy metabolism suggestive of enhanced hepatic β-oxidation. PMID:18925642

  16. Manual therapy ameliorates delayed-onset muscle soreness and alters muscle metabolites in rats.

    PubMed

    Urakawa, Susumu; Takamoto, Kouichi; Nakamura, Tomoya; Sakai, Shigekazu; Matsuda, Teru; Taguchi, Toru; Mizumura, Kazue; Ono, Taketoshi; Nishijo, Hisao

    2015-02-01

    Delayed-onset muscle soreness (DOMS) can be induced by lengthening contraction (LC); it can be characterized by tenderness and movement-related pain in the exercised muscle. Manual therapy (MT), including compression of exercised muscles, is widely used as physical rehabilitation to reduce pain and promote functional recovery. Although MT is beneficial for reducing musculoskeletal pain (i.e. DOMS), the physiological mechanisms of MT remain unclear. In the present study, we first developed an animal model of MT in DOMS; LC was applied to the rat gastrocnemius muscle under anesthesia, which induced mechanical hyperalgesia 2-4 days after LC. MT (manual compression) ameliorated mechanical hyperalgesia. Then, we used capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) to investigate early effects of MT on the metabolite profiles of the muscle experiencing DOMS. The rats were divided into the following three groups; (1) normal controls, (2) rats with LC application (LC group), and (3) rats undergoing MT after LC (LC + MT group). According to the CE-TOFMS analysis, a total of 171 metabolites were detected among the three groups, and 19 of these metabolites were significant among the groups. Furthermore, the concentrations of eight metabolites, including branched-chain amino acids, carnitine, and malic acid, were significantly different between the LC + MT and LC groups. The results suggest that MT significantly altered metabolite profiles in DOMS. According to our findings and previous data regarding metabolites in mitochondrial metabolism, the ameliorative effects of MT might be mediated partly through alterations in metabolites associated with mitochondrial respiration.

  17. Manual therapy ameliorates delayed-onset muscle soreness and alters muscle metabolites in rats

    PubMed Central

    Urakawa, Susumu; Takamoto, Kouichi; Nakamura, Tomoya; Sakai, Shigekazu; Matsuda, Teru; Taguchi, Toru; Mizumura, Kazue; Ono, Taketoshi; Nishijo, Hisao

    2015-01-01

    Delayed-onset muscle soreness (DOMS) can be induced by lengthening contraction (LC); it can be characterized by tenderness and movement-related pain in the exercised muscle. Manual therapy (MT), including compression of exercised muscles, is widely used as physical rehabilitation to reduce pain and promote functional recovery. Although MT is beneficial for reducing musculoskeletal pain (i.e. DOMS), the physiological mechanisms of MT remain unclear. In the present study, we first developed an animal model of MT in DOMS; LC was applied to the rat gastrocnemius muscle under anesthesia, which induced mechanical hyperalgesia 2–4 days after LC. MT (manual compression) ameliorated mechanical hyperalgesia. Then, we used capillary electrophoresis time-of-flight mass spectroscopy (CE-TOFMS) to investigate early effects of MT on the metabolite profiles of the muscle experiencing DOMS. The rats were divided into the following three groups; (1) normal controls, (2) rats with LC application (LC group), and (3) rats undergoing MT after LC (LC + MT group). According to the CE-TOFMS analysis, a total of 171 metabolites were detected among the three groups, and 19 of these metabolites were significant among the groups. Furthermore, the concentrations of eight metabolites, including branched-chain amino acids, carnitine, and malic acid, were significantly different between the LC + MT and LC groups. The results suggest that MT significantly altered metabolite profiles in DOMS. According to our findings and previous data regarding metabolites in mitochondrial metabolism, the ameliorative effects of MT might be mediated partly through alterations in metabolites associated with mitochondrial respiration. PMID:25713324

  18. Effect of a carbohydrate-protein multi-ingredient supplement on intermittent sprint performance and muscle damage in recreational athletes.

    PubMed

    Naclerio, Fernando; Larumbe-Zabala, Eneko; Cooper, Robert; Jimenez, Alfonso; Goss-Sampson, Mark

    2014-10-01

    Carbohydrate-protein-based multi-ingredient supplements have been proposed as an effective strategy for limiting the deleterious effects of exercise-induced muscle damage. This study compares the effects of a commercially available carbohydrate-protein supplement enriched with l-glutamine and l-carnitine-l-tartrate to carbohydrate alone or placebo on sprint performance, muscle damage markers, and recovery from intermittent exercise. On 3 occasions, 10 recreationally trained males ingested a multi-ingredient, a carbohydrate supplement, or a placebo before, during, and immediately after a 90-min intermittent repeated sprint test. Fifteen-metre sprint times, creatine kinase, myoglobin, and interleukin-6 were assessed before (pre), immediately after (post), 1 h after (1h), and 24 h after (24h) exercise. Total sprint time measured during the intermittent protocol was not different between conditions. Fifteen-metre sprint time was slower (p < 0.05) at post, 1h and 24h compared with pre without differences between conditions (p > 0.05). Creatine kinase at 24h was lower (p < 0.05) in the multi-ingredient (461.8 ± 271.8 U·L) compared with both carbohydrate and placebo (606 ± 314.5 U·L and 636 ± 344.6 U·L, respectively). Myoglobin increased (p < 0.05) in all 3 conditions at post and 1h compared with pre, showing lower values at 1h (p < 0.05) for the carbohydrate and a trend (p = 0.060) for multi-ingredient compared with the placebo condition (211.4 ± 127.2 ng·mL(-1) and 239.4 ± 103.8 ng·mL(-1) vs. 484.6 ± 200.0 ng·mL(-1), respectively). Interleukin-6 increased at both post and 1h compared with pre (p < 0.05) with no differences between conditions. In conclusion, ingesting a multi-ingredient supplement before, during, and immediately after a 90-min intermittent sprint test resulted in no effects on performance and fatigue while the accumulation of some biomarkers of muscle damage could be attenuated.

  19. Simulated Hypergravity Alters Vascular Smooth Muscle Cell Proliferation and Motility

    NASA Technical Reports Server (NTRS)

    Hunt, Shameka; Bettis, Barika; Harris-Hooker, Sandra; Sanford, Gary L.

    1997-01-01

    The cellular effects of gravity are poorly understood due to its constancy and nonavailability of altered gravitational models. Such an understanding is crucial for prolonged space flights. In these studies, we assessed the influence of centrifugation at 6G (HGrav) on vascular smooth muscle (SMC) mobility and proliferation. Cells were: (a) plated at low density and subjected to HGrav for 24-72 hr for proliferation studies, or (b) grown to confluency, subjected to HGrav, mechanically denuded and monitored for cell movement into the denuded area. Controls were maintained under normogravity. SMC showed a 50% inhibition of growth under HGrav and 10% serum; HGrav and low serum resulted in greater growth inhibition. The rate of movement of SMC into the denuded area was 2-3-fold higher under HGrav in low serum compared to controls, but similar in 10% serum. These studies show that HGrav has significant effects on SMC growth and mobility, which are dependent on serum levels.

  20. Simulated Hypergravity Alters Vascular Smooth Muscle Cell Proliferation and Motility

    NASA Technical Reports Server (NTRS)

    Hunt, Shameka; Bettis, Barika; Harris-Hooker, Sandra; Sanford, Gary L.

    1997-01-01

    The cellular effects of gravity are poorly understood due to its constancy and nonavailability of altered gravitational models. Such an understanding is crucial for prolonged space flights. In these studies, we assessed the influence of centrifugation at 6G (HGrav) on vascular smooth muscle (SMC) mobility and proliferation. Cells were: (a) plated at low density and subjected to HGrav for 24-72 hr for proliferation studies, or (b) grown to confluency, subjected to HGrav, mechanically denuded and monitored for cell movement into the denuded area. Controls were maintained under normogravity. SMC showed a 50% inhibition of growth under HGrav and 10% serum; HGrav and low serum resulted in greater growth inhibition. The rate of movement of SMC into the denuded area was 2-3-fold higher under HGrav in low serum compared to controls, but similar in 10% serum. These studies show that HGrav has significant effects on SMC growth and mobility, which are dependent on serum levels.

  1. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle

    PubMed Central

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-01

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling. PMID:26725948

  2. Cryotherapy Reduces Inflammatory Response Without Altering Muscle Regeneration Process and Extracellular Matrix Remodeling of Rat Muscle.

    PubMed

    Vieira Ramos, Gracielle; Pinheiro, Clara Maria; Messa, Sabrina Peviani; Delfino, Gabriel Borges; Marqueti, Rita de Cássia; Salvini, Tania de Fátima; Durigan, Joao Luiz Quagliotti

    2016-01-04

    The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

  3. Muscle fatigue in frog semitendinosus: alterations in contractile function

    NASA Technical Reports Server (NTRS)

    Thompson, L. V.; Balog, E. M.; Riley, D. A.; Fitts, R. H.

    1992-01-01

    The purpose of this study was to characterize the contractile properties of the frog semitendinosus (ST) muscle before and during recovery from fatigue, to relate the observed functional changes to alterations in specific steps in the crossbridge model of muscle contraction, and to determine how fatigue affects the force-frequency relationship. The frog ST (22 degrees C) was fatigued by direct electrical stimulation with 100-ms 150-Hz trains at 1/s for 5 min. The fatigue protocol reduced peak twitch (Pt) and tetanic (Po) force to 32 and 8.5% of initial force, respectively. The decline in Pt was less than Po, in part due to a prolongation in the isometric contraction time (CT), which increased to 300% of the initial value. The isometric twitch duration was greatly prolonged as reflected by the lengthened CT and the 800% increase in the one-half relaxation time (1/2RT). Both Pt and Po showed a biphasic recovery, a rapid initial phase (2 min) followed by a slower (40 min) return to the prefatigue force. CT and 1/2RT also recovered in two phases, returning to 160 and 265% of control in the first 5 min. CT returned to the prefatigue value between 35 and 40 min, whereas even at 60 min 1/2RT was 133% of control. The maximal velocity of shortening, determined by the slack test, was significantly reduced [from 6.7 +/- 0.5 to 2.5 +/- 0.4 optimal muscle length/s] at fatigue. The force-frequency relationship was shifted to the left, so that optimal frequency for generating Po was reduced.(ABSTRACT TRUNCATED AT 250 WORDS).

  4. Effects of exercise training on carbohydrate and lipid catabolism in the swimming muscles of Nile tilapia (Oreochromis niloticus).

    PubMed

    Li, D; Wei, X L; Lin, X T; Xu, Z N; Mu, X P

    2015-10-01

    This study aims to determine the effects of exercise training on carbohydrate and lipid catabolism in the swimming muscles of Nile tilapia (Oreochromis niloticus) by measuring the levels of related enzymes, lipids and free fatty acids. We designed one control group and two training groups of fish that were exercised at different training intensities [0, 1 and 1.5 body lengths per second (bl/s)]. The fish in the experimental groups were trained for 12 h/day for 4 weeks. Compared with the control group, the 1 and 1.5 bl/s groups showed significantly increased hexokinase and pyruvate kinase activities in red muscle (p < 0.05). In white muscle, pyruvate kinase activity was significantly higher in the 1.5 bl/s group than in the control group (p < 0.05), and hexokinase activity did not significantly differ between the groups. The activities of hormone-sensitive lipase and carnitine palmitoyltransferase I in both muscle types were significantly lower in the training groups than in the control group (p < 0.05). The plasma-free fatty acid level decreased (p < 0.05), while the lipid percentages increased in red muscle (p < 0.05) after exercise training. These findings clearly indicated that with exercise training, glycolysis increased and lipid oxidation decreased in the swimming muscle of tilapia. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  5. Muscle Carnosine Concentration with the Co-Ingestion of Carbohydrate with β-alanine in Male Rats.

    PubMed

    Naderi, Alireza; Sadeghi, Mehdi; Sarshin, Amir; Imanipour, Vahid; Nazeri, Seyed Ali; Farkhayi, Fatemeh; Willems, Mark E T

    2017-07-04

    Muscle carnosine is an intracellular buffer. The intake of β-alanine, combined with carbohydrate and protein, enhanced carnosine loading in human muscle. The aim of the present study was to examine if muscle carnosine loading was enhanced by β-alanine intake and co-ingestion of glucose in male rats. Thirty-six male rats were divided into three groups and supplemented for four weeks: β-alanine (βA group, 1.8% β-alanine in drinking water), β-alanine and glucose (βAGL group, 1.8% β-alanine and 5% glucose in drinking water), and control (C group, drinking water). During the supplementation period, rats were exercised (20 m·min(-1), 10 min·day(-1), 4 days·week(-1) for 4 weeks). Muscle carnosine concentration was quantified in soleus (n = 12) and rectus femoris (n = 6) muscles using high-performance liquid chromatography. In soleus muscle, carnosine concentration was 2.24 ± 1.10, 6.12 ± 1.08, and 6.93 ± 2.56 mmol/kg dw for control, βA, and βAGL, respectively. In rectus femoris, carnosine concentration was 2.26 ± 1.31, 7.90 ± 1.66, and 8.59 ± 2.33 mmol/kg dw for control, βA, and βAGL respectively. In each muscle, βA and βAGL resulted in similar carnosine increases compared to the control. In conclusion, β-alanine intake for four weeks, either alone or with glucose co-ingestion, equally increased muscle carnosine content. It appears that the potential insulin response to fluid glucose intake does not affect muscle carnosine loading in male rats.

  6. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    SciTech Connect

    Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.; and others

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  7. Altered Carbohydrates Allocation by Associated Bacteria-fungi Interactions in a Bark Beetle-microbe Symbiosis.

    PubMed

    Zhou, Fangyuan; Lou, Qiaozhe; Wang, Bo; Xu, Letian; Cheng, Chihang; Lu, Min; Sun, Jianghua

    2016-02-03

    Insect-microbe interaction is a key area of research in multiplayer symbiosis, yet little is known about the role of microbe-microbe interactions in insect-microbe symbioses. The red turpentine beetle (RTB) has destroyed millions of healthy pines in China and forms context-dependent relationships with associated fungi. The adult-associated fungus Leptographium procerum have played key roles in RTB colonization. However, common fungal associates (L. procerum and Ophiostoma minus) with RTB larvae compete for carbohydrates. Here, we report that dominant bacteria associated with RTB larvae buffer the competition by inhibiting the growth and D-glucose consumption of O. minus. However, they didn't inhibit the growth of L. procerum and forced this fungus to consume D-pinitol before consuming D-glucose, even though D-glucose was available and a better carbon source not only for L. procerum but also for RTB larvae and associated bacteria. This suggests the most frequently isolated bacteria associated with RTB larvae could affect fungal growth and the sequence of carbohydrate consumption. Thus, this regulates carbohydrate allocation in the RTB larva-microbe community, which may in turn benefit RTB larvae development. We also discuss the mechanism of carbohydrate allocation in the RTB larva-microbe community, and its potential contribution to the maintenance of a symbiotic community.

  8. Altered Carbohydrates Allocation by Associated Bacteria-fungi Interactions in a Bark Beetle-microbe Symbiosis

    PubMed Central

    Zhou, Fangyuan; Lou, Qiaozhe; Wang, Bo; Xu, Letian; Cheng, Chihang; Lu, Min; Sun, Jianghua

    2016-01-01

    Insect-microbe interaction is a key area of research in multiplayer symbiosis, yet little is known about the role of microbe-microbe interactions in insect-microbe symbioses. The red turpentine beetle (RTB) has destroyed millions of healthy pines in China and forms context-dependent relationships with associated fungi. The adult-associated fungus Leptographium procerum have played key roles in RTB colonization. However, common fungal associates (L. procerum and Ophiostoma minus) with RTB larvae compete for carbohydrates. Here, we report that dominant bacteria associated with RTB larvae buffer the competition by inhibiting the growth and D-glucose consumption of O. minus. However, they didn’t inhibit the growth of L. procerum and forced this fungus to consume D-pinitol before consuming D-glucose, even though D-glucose was available and a better carbon source not only for L. procerum but also for RTB larvae and associated bacteria. This suggests the most frequently isolated bacteria associated with RTB larvae could affect fungal growth and the sequence of carbohydrate consumption. Thus, this regulates carbohydrate allocation in the RTB larva-microbe community, which may in turn benefit RTB larvae development. We also discuss the mechanism of carbohydrate allocation in the RTB larva-microbe community, and its potential contribution to the maintenance of a symbiotic community. PMID:26839264

  9. Influences of carbohydrate plus amino acid supplementation on differing exercise intensity adaptations in older persons: skeletal muscle and endocrine responses

    PubMed Central

    Breen, Leigh; Stewart, Claire E.

    2010-01-01

    Losses in physiological function in healthy ageing occur partly as a consequence of reduced protein intake and partly as a consequence of less than 30-min/day of moderate to vigorous physical activity. The current study aimed to compare the effects of two different intensities of resistance training in healthy older adults, whose habitual dietary intake was supplemented with carbohydrate and amino acid preparations. We hypothesised that although intensive exercise with appropriate carbohydrate and amino acid supplementation would result in the most profound impact on in vivo markers of healthy physiologic and endocrine functions in previously sedentary older individuals, the effectiveness of the less intense exercise prescription with supplementation would also result in beneficial adaptations over and above findings of previous studies on low intensity exercise alone. Twenty-nine older adults (out of 32) completed the study after being randomly assigned to low (SUP_LowR, i.e., ∼40% 1RM; n = 16) versus high resistance training (SUP_HighR, i.e., ∼80% 1RM; n = 13) for 12 weeks. A carbohydrate supplement was ingested immediately before and during every exercise session and an amino acid cocktail was ingested post-exercise. Neither intervention significantly impacted upon body composition assessed using: Body mass index, waist/hip ratio and bioelectric impedance. Muscle strength increased similarly in the two groups with the SUP_HighR protocol showing 46 ± 8%, 10.8 ± 4.4% and 26.9 ± 4.9% (P < 0.01) improvements in 1-RM strength, unilateral and bilateral knee extension torque, respectively, compared with 39 ± 2%, 9.4 ± 3.7% and 29.5 ± 8.2% (P < 0.01) increments in the same measures in the SUP_LowR group. Lean muscle thickness however, showed a greater benefit of the SUP_LowR protocol (8.7 ± 3.9% increase, P < 0.05) compared with the SUP_HighR protocol, which elicited no significant change. In terms of

  10. Changes in skeletal muscle gene expression consequent to altered weight bearing

    NASA Technical Reports Server (NTRS)

    Booth, F. W.; Kirby, C. R.

    1992-01-01

    Skeletal muscle is a dynamic organ that adapts to alterations in weight bearing. This brief review examines changes in muscle gene expression resulting from the removal of weight bearing by hindlimb suspension and from increased weight bearing due to eccentric exercise. Acute (less than or equal to 2 days) non-weight bearing of adult rat soleus muscle alters only the translational control of muscle gene expression, while chronic (greater than or equal to 7 days) removal of weight bearing appears to influence pretranslational, translational, and posttranslational mechanisms of control. Acute and chronic eccentric exercise are associated with alterations of translational and posttranslational control, while chronic eccentric training also alters the pretranslational control of muscle gene expression. Thus alterations in weight bearing influence multiple sites of gene regulation.

  11. Enhanced muscle strength with carbohydrate supplement two hours before open cholecystectomy: a randomized, double-blind study.

    PubMed

    Gava, Marcella Giovana; Castro-Barcellos, Heloísa Michelon; Caporossi, Cervantes; Aguilar-Nascimento, José Eduardo de

    2016-02-01

    to investigate the effects of preoperative fasting abbreviation with oral supplementation with carbohydrate in the evolution of grip strength in patients undergoing cholecystectomy by laparotomy. we conducted a clinical, randomizeddouble blind study with adult female patients, aged 18-60 years. Patients were divided into two groups: Control Group, with fasting prescription 6-8h until the time of operation; and Intervention Group, which received prescription of fasting for solids 6-8h before surgery, but ingested an oral supplement containing 12.5% carbohydrate, six (400ml) and two (200ml) hours before theprocedure. The handgrip strength was measured in both hands in both groups, at patient's admission (6h before surgery), the immediate pre-operative time (1h before surgery) and 12-18h postoperatively. we analyzed 27 patients, 14 in the intervention group and 13 in the control group. There was no mortality. The handgrip strength (mean [standard deviation]) was significantly higher in the intervention group in the three periods studied, in at least one hand: preoperatively in the dominant hand (27.8 [2.6] vs 24.1 [3.7] kg; p=0.04), in the immediate preoperative in both hands, and postoperatively in the non-dominant hand (28.5 [3.0] vs 21.3 [5.9] kg; p=0.01). the abbreviation of preoperative fasting to two hours with drink containing carbohydrate improves muscle function in the perioperative period.

  12. Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

    PubMed

    Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

    2015-03-01

    The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats.

  13. Altered reward value of carbohydrate snacks for female smokers withdrawn from nicotine.

    PubMed

    Spring, Bonnie; Pagoto, Sherry; McChargue, Dennis; Hedeker, Donald; Werth, Jessica

    2003-09-01

    Discontinuing nicotine intake usually results in weight gain partially due to heightened energy intake from between-meal snacks. This experiment tested the hypothesis that the reinforcing value of palatable carbohydrate-rich snacks increases for female smokers during nicotine deprivation. Eighteen smokers and 18 nonsmokers completed a concurrent-schedules operant computer task on two separate days. Smokers were bioverified abstinent at the second testing. The operant task allowed participants to earn points redeemable for either carbohydrate snacks or money on concurrent variable-ratio schedules of reinforcement. There were five different probabilities of earning points redeemable for snacks (8%, 16%, 25%, 50%, 75%), while the probability of earning points redeemable for money remained fixed at 25%. Reward value of snacks was measured by switch point: the reinforcement ratio at which the effort required to earn snacks exceeded their value to the respondent, as signified by a shift to working for money. Results showed that smokers undergoing nicotine deprivation persisted in working for snacks into leaner reinforcement schedules than nonsmokers (P=.026). Furthermore, nicotine deprivation increased smokers' allocation of effort to earn snack foods relative to their own behavior when smoking (P=.006). Variation in palatability or hunger did not explain these differences in snack reward value. Findings indicate that nicotine deprivation is associated with a heightened reward value of appealing snack foods for female smokers.

  14. Mechanically induced alterations in cultured skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.; Hatfaludy, S.; Karlisch, P.; Shansky, J.

    1991-01-01

    Model systems are available for mechanically stimulating cultured skeletal muscle cells by passive tensile forces which simulate those found in vivo. When applied to embryonic muscle cells in vitro these forces induce tissue organogenesis, metabolic adaptations, and muscle cell growth. The mechanical stimulation of muscle cell growth correlates with stretch-induced increases in the efflux of prostaglandins PGE2 and PGF2(alpha) in a time and frequency dependent manner. These prostaglandins act as mechanical 'second messengers' regulating skeletal muscle protein turnover rates. Since they also effect bone remodelling in response to tissue loading and unloading, secreted prostaglandins may serve as paracrine growth factors, coordinating the growth rates of muscle and bone in response to external mechanical forces. Cell culture model systems will supplement other models in understanding mechanical transduction processes at the molecular level.

  15. Mechanically induced alterations in cultured skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.; Hatfaludy, S.; Karlisch, P.; Shansky, J.

    1991-01-01

    Model systems are available for mechanically stimulating cultured skeletal muscle cells by passive tensile forces which simulate those found in vivo. When applied to embryonic muscle cells in vitro these forces induce tissue organogenesis, metabolic adaptations, and muscle cell growth. The mechanical stimulation of muscle cell growth correlates with stretch-induced increases in the efflux of prostaglandins PGE2 and PGF2(alpha) in a time and frequency dependent manner. These prostaglandins act as mechanical 'second messengers' regulating skeletal muscle protein turnover rates. Since they also effect bone remodelling in response to tissue loading and unloading, secreted prostaglandins may serve as paracrine growth factors, coordinating the growth rates of muscle and bone in response to external mechanical forces. Cell culture model systems will supplement other models in understanding mechanical transduction processes at the molecular level.

  16. Alteration of the carbohydrate-binding specificity of a C-type lectin CEL-I mutant with an EPN carbohydrate-binding motif.

    PubMed

    Hatakeyama, Tomomitsu; Ishimine, Tomohiro; Baba, Tomohiro; Kimura, Masanari; Unno, Hideaki; Goda, Shuichiro

    2013-07-01

    CEL-I is a Gal/GalNAc-specific C-type lectin isolated from the sea cucumber Cucumaria echinata. This lectin is composed of two carbohydrate-recognition domains (CRDs) with the carbohydrate-recognition motif QPD (Gln-Pro- Asp), which is generally known to exist in galactose-specific C-type CRDs. In the present study, a mutant CEL-I with EPN (Glu-Pro-Asn) motif, which is thought to be responsible for the carbohydrate-recognition of mannose-specific Ctype CRDs, was produced in Escherichia coli, and its effects on the carbohydrate-binding specificity were examined using polyamidoamine dendrimer (PD) conjugated with carbohydrates. Although wild-type CEL-I effectively formed complexes with N-acetylgalactosamine (GalNAc)-PD but not with mannose-PD, the mutant CEL-I showed relatively weak but definite affinity for mannose-PD. These results indicated that the QPD and EPN motifs play a significant role in the carbohydrate-recognition mechanism of CEL-I, especially in the discrimination of galactose and mannose. Additional mutations in the recombinant CEL-I binding site may further increase its specificity for mannose, and should provide insights into designing novel carbohydrate-recognition proteins.

  17. Apparent low ability of liver and muscle to adapt to variation of dietary carbohydrate:protein ratio in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Skiba-Cassy, Sandrine; Panserat, Stéphane; Larquier, Mélanie; Dias, Karine; Surget, Anne; Plagnes-Juan, Elisabeth; Kaushik, Sadasivam; Seiliez, Iban

    2013-04-28

    The rainbow trout (Oncorhynchus mykiss) exhibits high dietary amino acid requirements and an apparent inefficiency to use dietary carbohydrates. Using this species, we investigated the metabolic consequences of long-term high carbohydrates/low protein feeding. Fish were fed two experimental diets containing either 20% carbohydrates/50% proteins (C20P50), or high levels of carbohydrates at the expense of proteins (35% carbohydrates/35% proteins--C35P35). The expression of genes related to hepatic and muscle glycolysis (glucokinase (GK), pyruvate kinase and hexokinase) illustrates the poor utilisation of carbohydrates irrespective of their dietary levels. The increased postprandial GK activity and the absence of inhibition of the gluconeogenic enzyme glucose-6-phosphatase activity support the hypothesis of the existence of a futile cycle around glucose phosphorylation extending postprandial hyperglycaemia. After 9 weeks of feeding, the C35P35-fed trout displayed lower body weight and feed efficiency and reduced protein and fat gains than those fed C20P50. The reduced activation of eukaryotic translation initiation factor 4-E binding protein 1 (4E-BP1) in the muscle in this C35P35 group suggests a reduction in protein synthesis, possibly contributing to the reduction in N gain. An increase in the dietary carbohydrate:protein ratio decreased the expression of genes involved in amino acid catabolism (serine dehydratase and branched-chain α-keto acid dehydrogenase E1α and E1β), and increased that of carnitine palmitoyltransferase 1, suggesting a higher reliance on lipids as energy source in fish fed high-carbohydrate and low-protein diets. This probably also contributes to the lower fat gain. Together, these results show that different metabolic pathways are affected by a high-carbohydrate/low-protein diet in rainbow trout.

  18. Fermentable carbohydrate alters hypothalamic neuronal activity and protects against the obesogenic environment.

    PubMed

    Anastasovska, Jelena; Arora, Tulika; Sanchez Canon, Gina J; Parkinson, James R C; Touhy, Kieran; Gibson, Glen R; Nadkarni, Nachiket A; So, Po-Wah; Goldstone, Anthony P; Thomas, E Louise; Hankir, Mohammed K; Van Loo, Jan; Modi, Neena; Bell, Jimmy D; Frost, Gary

    2012-05-01

    Obesity has become a major global health problem. Recently, attention has focused on the benefits of fermentable carbohydrates on modulating metabolism. Here, we take a system approach to investigate the physiological effects of supplementation with oligofructose-enriched inulin (In). We hypothesize that supplementation with this fermentable carbohydrate will not only lead to changes in body weight and composition, but also to modulation in neuronal activation in the hypothalamus. Male C57BL/6 mice were maintained on a normal chow diet (control) or a high fat (HF) diet supplemented with either oligofructose-enriched In or corn starch (Cs) for 9 weeks. Compared to HF+Cs diet, In supplementation led to significant reduction in average daily weight gain (mean ± s.e.m.: 0.19 ± 0.01 g vs. 0.26 ± 0.02 g, P < 0.01), total body adiposity (24.9 ± 1.2% vs. 30.7 ± 1.4%, P < 0.01), and lowered liver fat content (11.7 ± 1.7% vs. 23.8 ± 3.4%, P < 0.01). Significant changes were also observed in fecal bacterial distribution, with increases in both Bifidobacteria and Lactobacillius and a significant increase in short chain fatty acids (SCFA). Using manganese-enhanced MRI (MEMRI), we observed a significant increase in neuronal activation within the arcuate nucleus (ARC) of animals that received In supplementation compared to those fed HF+Cs diet. In conclusion, we have demonstrated for the first time, in the same animal, a wide range of beneficial metabolic effects following supplementation of a HF diet with oligofructose-enriched In, as well as significant changes in hypothalamic neuronal activity.

  19. Alterations in innate immunity reactants and carbohydrate and lipid metabolism precede occurrence of metritis in transition dairy cows.

    PubMed

    Dervishi, Elda; Zhang, Guanshi; Hailemariam, Dagnachew; Goldansaz, Seyed Ali; Deng, Qilan; Dunn, Suzanna M; Ametaj, Burim N

    2016-02-01

    The overall purpose of the present study was to search for early screening biomarkers of disease state. Therefore the objectives of this study were to evaluate metabolites related to carbohydrate metabolism, acute phase proteins, and proinflammatory cytokines in the blood of transition dairy cows starting at -8 weeks before calving. Blood samples were collected from 100 multiparous Holstein dairy cows during -8, -4, disease diagnosis, +4 and +8 weeks relative to parturition. Six healthy cows and 6 cows that showed clinical signs of metritis were selected for serum analysis. Overall the results showed that cows with metritis had greater concentration of lactate, interleukin-6 (IL-6), tumor necrosis factor (TNF), and serum amyloid A (SAA) versus healthy cows throughout the experiment. The disease was associated with decrease in milk production and fat: protein ratio. Cows with metritis showed alteration in metabolites related to carbohydrate metabolism, acute phase proteins, and proinflammatory cytokines starting at -8 weeks prior to parturition and appearance of clinical signs of the disease. This study suggests a possible use of cytokines as early markers of disease in dairy cows.

  20. Preexercise carbohydrate ingestion, glucose kinetics, and muscle glycogen use: effect of the glycemic index.

    PubMed

    Febbraio, M A; Keenan, J; Angus, D J; Campbell, S E; Garnham, A P

    2000-11-01

    Eight trained men cycled at 70% peak oxygen uptake for 120 min followed by a 30-min performance cycle after ingesting either a high-glycemic index (HGI), low-glycemic index (LGI), or placebo (Con) meal 30 min before exercise. Ingestion of HGI resulted in an elevated (P<0.01) blood glucose concentration compared with LGI and Con. At the onset of exercise, blood glucose fell (P<0.05) such that it was lower (P<0.05) in HGI compared with LGI and Con at 15 and 30 min during exercise. Plasma insulin concentration was higher (P<0.01) throughout the rest period after ingestion of HGI compared with LGI and Con. Plasma free fatty acid concentrations were lower (P<0.05) throughout exercise in HGI compared with LGI and Con. The rates of [6,6-(2)H]glucose appearance and disappearance were higher (P<0.05) at rest after ingestion and throughout exercise in HGI compared with LGI and Con. Carbohydrate oxidation was higher (P<0.05) throughout exercise, whereas glycogen use tended (P = 0.07) to be higher in HGI compared with LGI and Con. No differences were observed in work output during the performance cycle when comparing the three trials. These results demonstrate that preexercise carbohydrate feeding with a HGI, but not a LGI, meal augments carbohydrate utilization during exercise but does not effect exercise performance.

  1. High and low protein∶ carbohydrate dietary ratios during gestation alter maternal-fetal cortisol regulation in pigs.

    PubMed

    Kanitz, Ellen; Otten, Winfried; Tuchscherer, Margret; Gräbner, Maria; Brüssow, Klaus-Peter; Rehfeldt, Charlotte; Metges, Cornelia C

    2012-01-01

    Imbalanced maternal nutrition during gestation can cause alterations of the hypothalamic-pituitary-adrenal (HPA) system in offspring. The present study investigated the effects of maternal low- and high-protein diets during gestation in pigs on the maternal-fetal HPA regulation and expression of the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD1 and 11β-HSD2) and c-fos mRNAs in the placenta and fetal brain. Twenty-seven German Landrace sows were fed diets with high (HP, 30%), low (LP, 6.5%) or adequate (AP, 12.1%) protein levels made isoenergetic by varying the carbohydrate levels. On gestational day 94, fetuses were recovered under general anesthesia for the collection of blood, brain and placenta samples. The LP diet in sows increased salivary cortisol levels during gestation compared to the HP and AP sows and caused an increase of placental GR and c-fos mRNA expression. However, the diurnal rhythm of plasma cortisol was disturbed in both LP and HP sows. Total plasma cortisol concentrations in the umbilical cord vessels were elevated in fetuses from HP sows, whereas corticosteroid-binding globulin levels were decreased in LP fetuses. In the hypothalamus, LP fetuses displayed an enhanced mRNA expression of 11β-HSD1 and a reduced expression of c-fos. Additionally, the 11β-HSD2 mRNA expression was decreased in both LP and HP fetuses. The present results suggest that both low and high protein∶carbohydrate dietary ratios during gestation may alter the expression of genes encoding key determinants of glucocorticoid hormone action in the fetus with potential long-lasting consequences for stress adaptation and health.

  2. Aging alters contractile properties and fiber morphology in pigeon skeletal muscle.

    PubMed

    Pistilli, Emidio E; Alway, Stephen E; Hollander, John M; Wimsatt, Jeffrey H

    2014-12-01

    In this study, we tested the hypothesis that skeletal muscle from pigeons would display age-related alterations in isometric force and contractile parameters as well as a shift of the single muscle fiber cross-sectional area (CSA) distribution toward smaller fiber sizes. Maximal force output, twitch contraction durations and the force-frequency relationship were determined in tensor propatagialis pars biceps muscle from young 3-year-old pigeons, middle-aged 18-year-old pigeons, and aged 30-year-old pigeons. The fiber CSA distribution was determined by planimetry from muscle sections stained with hematoxylin and eosin. Maximal force output of twitch and tetanic contractions was greatest in muscles from young pigeons, while the time to peak force of twitch contractions was longest in muscles from aged pigeons. There were no changes in the force-frequency relationship between the age groups. Interestingly, the fiber CSA distribution in aged muscles revealed a greater number of larger sized muscle fibers, which was verified visually in histological images. Middle-aged and aged muscles also displayed a greater amount of slow myosin containing muscle fibers. These data demonstrate that muscles from middle-aged and aged pigeons are susceptible to alterations in contractile properties that are consistent with aging, including lower force production and longer contraction durations. These functional changes were supported by the appearance of slow myosin containing muscle fibers in muscles from middle-aged and aged pigeons. Therefore, the pigeon may represent an appropriate animal model for the study of aging-related alterations in skeletal muscle function and structure.

  3. Phosphocreatine degradation in type I and type II muscle fibres during submaximal exercise in man: effect of carbohydrate ingestion.

    PubMed

    Tsintzas, K; Williams, C; Constantin-Teodosiu, D; Hultman, E; Boobis, L; Clarys, P; Greenhaff, P

    2001-11-15

    1. The aim of this study was to examine the effect of carbohydrate (CHO) ingestion on changes in ATP and phosphocreatine (PCr) concentrations in different muscle fibre types during prolonged running and relate those changes to the degree of glycogen depletion. 2. Five male subjects performed two runs at 70 % maximum oxygen uptake (.V(O2,max)), 1 week apart. Each subject ingested 8 ml (kg body mass (BM))(-1) of either a placebo (Con trial) or a 5.5 % CHO solution (CHO trial) immediately before each run and 2 ml (kg BM)(-1) every 20 min thereafter. In the Con trial, the subjects ran to exhaustion (97.0 +/- 6.7 min). In the CHO trial, the run was terminated at the time coinciding with exhaustion in the Con trial. Muscle samples were obtained from the vastus lateralis before and after each trial. 3. Carbohydrate ingestion did not affect ATP concentrations. However, it attenuated the decline in PCr concentration by 46 % in type I fibres (CHO: 20 +/- 8 mmol (kg dry matter (DM))(-1); Con: 34 +/- 6 mmol (kg DM)(-1); P < 0.05) and by 36 % in type II fibres (CHO: 30 +/- 5 mmol (kg DM)(-1); Con: 48 +/- 6 mmol (kg DM)(-1); P < 0.05). 4. A 56 % reduction in glycogen utilisation in type I fibres was observed in CHO compared with Con (117 +/- 39 vs. 240 +/- 32 mmol glucosyl units (kg DM)(-1), respectively; P < 0.01), but no difference was observed in type II fibres. 5. It is proposed that CHO ingestion during exhaustive running attenuates the decline in oxidative ATP resynthesis in type I fibres, as indicated by sparing of both PCr and glycogen breakdown. The CHO-induced sparing of PCr, but not glycogen, in type II fibres may reflect differential recruitment and/or role of PCr between fibre types.

  4. Tissue sorbitol concentration can be altered by changing the type of dietary carbohydrate or copper status

    SciTech Connect

    Beal, T.; Lewis, C.G.; Fields, M. )

    1989-02-09

    This study was designed to determine whether rehabilitation of tissue sorbitol concentration occurs when rats consuming a high-fructose, low-copper diet are changed to diets containing starch or copper. Weanling male rats were provided with a diet which contained 62.7% fructose and 0.6 or 6.0 {mu}g Cu/g (F-Cu) for 4 weeks and then changed to either a fructose diet which contained 6.0 {mu}g Cu/g or a starch diet which contained either 0.6 or 6.0 {mu}g Cu/g for 2 weeks. Hepatic copper concentration of rats eating copper-deficient diets was about 30% of copper adequate rats regardless of the type of dietary carbohydrate. Pancreatic fructose, glucose and sorbitol concentrations were significantly lowered in rats changed to a starch diet. Kidney fructose and sorbitol concentrations were significantly lowered in rats changed to a starch diet. For all dietary groups, pancreatic and kidney sorbitol concentrations returned to normal after removal of rats from the F-Cu diet. In general, changing rats from a high-fructose, low-copper diet to a fructose diet with copper or a starch diet with or without copper improved the copper deficiency symptoms which changed in concert with tissue sorbitol levels.

  5. Altered microRNA expression in bovine skeletal muscle with age

    USDA-ARS?s Scientific Manuscript database

    Age dependent decline in skeletal muscle function leads to several inherited and acquired muscular disorders in elderly individuals. The levels of microRNAs (miRNAs) could be altered during muscle maintenance and repair. Therefore, we performed a comprehensive investigation for miRNAs from 5 differe...

  6. Altered Macrophage Phenotype Transition Impairs Skeletal Muscle Regeneration

    PubMed Central

    Wang, Hanzhou; Melton, David W.; Porter, Laurel; Sarwar, Zaheer U.; McManus, Linda M.; Shireman, Paula K.

    2015-01-01

    Monocyte/macrophage polarization in skeletal muscle regeneration is ill defined. We used CD11b-diphtheria toxin receptor transgenic mice to transiently deplete monocytes/macrophages at multiple stages before and after muscle injury induced by cardiotoxin. Fat accumulation within regenerated muscle was maximal when ablation occurred at the same time as cardiotoxin-induced injury. Early ablation (day 1 after cardiotoxin) resulted in the smallest regenerated myofiber size together with increased residual necrotic myofibers and fat accumulation. However, muscle regeneration after late (day 4) ablation was similar to controls. Levels of inflammatory cells in injured muscle following early ablation and associated with impaired muscle regeneration were determined by flow cytometry. Delayed, but exaggerated, monocyte [CD11b+(CD90/B220/CD49b/NK1.1/Ly6G)−(F4/80/I-Ab/CD11c)−Ly6C+/−] accumulation occurred; interestingly, Ly6C+ and Ly6C− monocytes were present concurrently in ablated animals and control mice. In addition to monocytes, proinflammatory, Ly6C+ macrophage accumulation following early ablation was delayed compared to controls. In both groups, CD11b+F4/80+ cells exhibited minimal expression of the M2 markers CD206 and CD301. Nevertheless, early ablation delayed and decreased the transient accumulation of CD11b+F4/80+Ly6C−CD301− macrophages; in control animals, the later tissue accumulation of these cells appeared to correspond to that of anti-inflammatory macrophages, determined by cytokine production and arginase activity. In summary, impairments in muscle regeneration were associated with exaggerated monocyte recruitment and reduced Ly6C− macrophages; the switch of macrophage/monocyte subsets is critical to muscle regeneration. PMID:24525152

  7. Resistance Exercise Training Alters Mitochondrial Function in Human Skeletal Muscle.

    PubMed

    Porter, Craig; Reidy, Paul T; Bhattarai, Nisha; Sidossis, Labros S; Rasmussen, Blake B

    2015-09-01

    Loss of mitochondrial competency is associated with several chronic illnesses. Therefore, strategies that maintain or increase mitochondrial function will likely be of benefit in numerous clinical settings. Endurance exercise has long been known to increase mitochondrial function in the skeletal muscle. Comparatively little is known regarding the effect of resistance exercise training (RET) on skeletal muscle mitochondrial respiratory function. The purpose of the current study was to determine the effect of chronic resistance training on skeletal muscle mitochondrial respiratory capacity and function. Here, we studied the effect of a 12-wk RET program on skeletal muscle mitochondrial function in 11 young healthy men. Muscle biopsies were collected before and after the 12-wk training program, and mitochondrial respiratory capacity was determined in permeabilized myofibers by high-resolution respirometry. RET increased lean body mass and quadriceps muscle strength by 4% and 15%, respectively (P < 0.001). Coupled mitochondrial respiration supported by complex I, and complex I and II substrates increased by 2- and 1.4-fold, respectively (P < 0.01). The ratio of coupled complex I-supported respiration to maximal respiration increased with RET (P < 0.05), as did complex I protein abundance (P < 0.05), whereas the substrate control ratio for succinate was reduced after RET (P < 0.001). Transcripts responsible for proteins critical to electron transfer and NAD production increased with training (P < 0.05), whereas transcripts involved in mitochondrial biogenesis were unaltered. Collectively, 12 wk of RET resulted in qualitative and quantitative changes in skeletal muscle mitochondrial respiration. This adaptation was accompanied by modest changes in mitochondrial proteins and transcript expression. RET seems to be a means to augment the respiratory capacity and intrinsic function of skeletal muscle mitochondria.

  8. Generating novel recombinant prokaryotic lectins with altered carbohydrate binding properties through mutagenesis of the PA-IL protein from Pseudomonas aeruginosa.

    PubMed

    Keogh, Damien; Thompson, Roisin; Larragy, Ruth; McMahon, Kenneth; O'Connell, Michael; O'Connor, Brendan; Clarke, Paul

    2014-06-01

    Prokaryotic lectins offer significant advantages over eukaryotic lectins for the development of enhanced glycoselective tools. Amenability to recombinant expression in Escherichia coli simplifies their production and presents opportunities for further genetic manipulation to create novel recombinant prokaryotic lectins (RPLs) with altered or enhanced carbohydrate binding properties. This study explored the potential of the α-galactophilic PA-IL lectin from Pseudomonas aeruginosa for use as a scaffold structure for the generation of novel RPLs. Specific amino acid residues in the carbohydrate binding site of a recombinant PA-IL protein were randomly substituted by site-directed mutagenesis. The resulting expression clones were then functionally screened to identify clones expressing rPA-IL proteins with altered carbohydrate binding properties. This study generated RPLs exhibiting diverse carbohydrate binding activities including specificity and high affinity for β-linked galactose and N-acetyl-lactosamine (LacNAc) displayed by N-linked glycans on glycoprotein targets. Key amino acid substitutions were identified and linked with specific carbohydrate binding activities. Ultimately, the utility of these novel RPLs for glycoprotein analysis and for selective fractionation and isolation of glycoproteins and their glycoforms was demonstrated. The carbohydrate binding properties of the PA-IL protein can be significantly altered using site-directed mutagenesis strategies to generate novel RPLs with diverse carbohydrate binding properties. The novel RPLs reported would find a broad range of applications in glycobiology, diagnostics and in the analysis of biotherapeutics. The ability to readily produce these RPLs in gram quantities could enable them to find larger scale applications for glycoprotein or biotherapeutic purification. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Effects of sustained swimming on the red and white muscle transcriptome of rainbow trout (Oncorhynchus mykiss) fed a carbohydrate-rich diet.

    PubMed

    Magnoni, Leonardo J; Crespo, Diego; Ibarz, Antoni; Blasco, Josefina; Fernández-Borràs, Jaume; Planas, Josep V

    2013-11-01

    Training at sustainable swimming speeds can produce changes in fish skeletal muscle that are important for aquaculture due to their growth-potentiating effects. Such changes may be even more relevant when fish are fed diets containing an increasing proportion of carbohydrates as an energy source. We evaluated the effects of moderate-intensity sustained swimming on the transcriptomic response of red and white muscle in rainbow trout fed a carbohydrate-rich diet using microarray and qPCR. Analysis of the red and white muscle transcriptome in resting or swimming (1.3 body lengths/s) fish for 30days revealed significant changes in the expression of a large number of genes (395 and 597, respectively), with a total of 218 differentially expressed genes (DEGs) common for both muscles. A large number of the genes involved in glucose use and energy generation, contraction, development, synthesis and catabolism of proteins were up-regulated in red and white muscle. Additionally, DEGs in both muscles were involved in processes of defense response and apoptosis. Skeletal muscle contraction activates a transcriptional program required for the successful adaptation of both muscles to the changing demands imposed by swimming conditions. Future studies should further clarify the mechanisms involved in the adaptation of both tissues to exercise and assess possible benefits of such conditions for cultured fish.

  10. Muscle and Liver Carbohydrates: Response to Military Task Performance by Women and Men

    DTIC Science & Technology

    2001-10-01

    the muscles of the lower leg, while the male population acclimatized to the exercise protocol and relied less on the hamstrings . 3) Over the course of...61: 165-172, 1986. JAP-00394-2002 17 10. Doyle, J.A., W.M. Sherman, and R.L. Strauss. Effects of eccentric and concentric exercise on muscle glycogen...data analysis and found that, unlike men, women work their lower legs harder during the latter stages of exercise than during the first hour. We have

  11. Prevention of metabolic alterations caused by suspension hypokinesia in leg muscles of rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Jaspers, S. R.; Fagan, J. M.

    1983-01-01

    Rats were subjected to tail-cast suspension hypokinesia for 6 days with one leg immobilized in dorsal flexion by casting. Control animals were also tail-casted. The soleus, gastrocnemius and plantaris muscles of uncasted hypokinetic legs were smaller than control muscles. Dorsal flexion prevented atrophy of these muscles and caused the soleus to hypertrophy. The anterior muscles were unaffected by hypokinesia. The smaller size of the soleus of the uncasted leg relative to the dorsal flexed and weight bearing limbs correlated with slower protein synthesis and faster proteolysis. The capacity of this muscle to synthesize glutamine (gln), which carries nitrogenous waste from muscle was also measured. Although tissue homogenates showed higher activities of gln synthetase, the rate of de novo synthesis was not altered in intact muscle but the tissue ratio of gln/glutamate was decreased. Glutamate and ATP were not limiting for gln synthesis, but availability of ammonia may be a limiting factor for this process in hypokinesia.

  12. Prevention of metabolic alterations caused by suspension hypokinesia in leg muscles of rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Jaspers, S. R.; Fagan, J. M.

    1983-01-01

    Rats were subjected to tail-cast suspension hypokinesia for 6 days with one leg immobilized in dorsal flexion by casting. Control animals were also tail-casted. The soleus, gastrocnemius and plantaris muscles of uncasted hypokinetic legs were smaller than control muscles. Dorsal flexion prevented atrophy of these muscles and caused the soleus to hypertrophy. The anterior muscles were unaffected by hypokinesia. The smaller size of the soleus of the uncasted leg relative to the dorsal flexed and weight bearing limbs correlated with slower protein synthesis and faster proteolysis. The capacity of this muscle to synthesize glutamine (gln), which carries nitrogenous waste from muscle was also measured. Although tissue homogenates showed higher activities of gln synthetase, the rate of de novo synthesis was not altered in intact muscle but the tissue ratio of gln/glutamate was decreased. Glutamate and ATP were not limiting for gln synthesis, but availability of ammonia may be a limiting factor for this process in hypokinesia.

  13. Coingestion of protein with carbohydrate during recovery from endurance exercise stimulates skeletal muscle protein synthesis in humans.

    PubMed

    Howarth, Krista R; Moreau, Natalie A; Phillips, Stuart M; Gibala, Martin J

    2009-04-01

    Coingestion of protein with carbohydrate (CHO) during recovery from exercise can affect muscle glycogen synthesis, particularly if CHO intake is suboptimal. Another potential benefit of protein feeding is an increased synthesis rate of muscle proteins, as is well documented after resistance exercise. In contrast, the effect of nutrient manipulation on muscle protein kinetics after aerobic exercise remains largely unexplored. We tested the hypothesis that ingesting protein with CHO after a standardized 2-h bout of cycle exercise would increase mixed muscle fractional synthetic rate (FSR) and whole body net protein balance (WBNB) vs. trials matched for total CHO or total energy intake. We also examined whether postexercise glycogen synthesis could be enhanced by adding protein or additional CHO to a feeding protocol that provided 1.2 g CHO x kg(-1) x h(-1), which is the rate generally recommended to maximize this process. Six active men ingested drinks during the first 3 h of recovery that provided either 1.2 g CHO.kg(-1).h(-1) (L-CHO), 1.2 g CHO + 0.4 g protein x kg(-1) x h(-1) (PRO-CHO), or 1.6 g CHO x kg(-1) x h(-1) (H-CHO) in random order. Based on a primed constant infusion of l-[ring-(2)H(5)]phenylalanine, analysis of biopsies (vastus lateralis) obtained at 0 and 4 h of recovery showed that muscle FSR was higher (P < 0.05) in PRO-CHO (0.09 +/- 0.01%/h) vs. both L-CHO (0.07 +/- 0.01%/h) and H-CHO (0.06 +/- 0.01%/h). WBNB assessed using [1-(13)C]leucine was positive only during PRO-CHO, and this was mainly attributable to a reduced rate of protein breakdown. Glycogen synthesis rate was not different between trials. We conclude that ingesting protein with CHO during recovery from aerobic exercise increased muscle FSR and improved WBNB, compared with feeding strategies that provided CHO only and were matched for total CHO or total energy intake. However, adding protein or additional CHO to a feeding strategy that provided 1.2 g CHO x kg(-1) x h(-1) did not further

  14. Muscle volume alterations in spastic muscles immediately following botulinum toxin type-A treatment in children with cerebral palsy.

    PubMed

    Williams, Sîan A; Reid, Siobhan; Elliott, Catherine; Shipman, Peter; Valentine, Jane

    2013-09-01

    With evidence for an atrophic effect of botulinum toxin type A (BoNT-A) documented in typically developing muscles, this study investigated the immediate morphological alterations of muscles in children with cerebral palsy (CP) after BoNT-A treatment. Fifteen children (10 males, five females; age range 5-11y, mean age 8y 5mo, SD 1y 10mo) with spastic diplegic CP [Gross Motor Function Classification System Levels I (n=9) and II (n=6)] receiving BoNT-A injections for spasticity management were included. None of the children was a first-time receiver of BoNT-A. Magnetic resonance imaging and Mimics software assessed muscle volume, timed 2 weeks before and 5 weeks after injection. All participants received BoNT-A bilaterally to the gastrocnemius muscle, and five participants also received BoNT-A bilaterally to the medial hamstring muscles. Functional assessment measures used were the 6-Minute Walk Test (6-MWT), the Timed Up and Go (TUG) test, and hand-held dynamometry. Whilst total muscle group volume of the injected muscle group remained unchanged, a 4.47% decrease in the injected gastrocnemius muscle volume (p=0.01) and a 3.96% increase in soleus muscle volume (p=0.02) was evident following BoNT-A. There were no statistically significant changes in function after BoNT-A as assessed by the TUG. There was also no statistically significant change in distance covered in the 6-MWT. Muscle strength, as assessed using hand-held dynamometry was also not statistically different after BoNT-A treatment. Muscle volume decreases were observed in the injected muscle (gastrocnemius), with synergistic muscle hypertrophy that appeared to compensate for this decrement. The 4% to 5% decrease in the volume of BoNT-A injected muscles are not dramatic in comparison to reports in recent animal studies, and are a positive indication for BoNT-A, particularly as it also did not negatively alter function. © 2013 Mac Keith Press.

  15. Postprandial heat production in skeletal muscle is associated with altered mitochondrial function and altered futile calcium cycling.

    PubMed

    Clarke, Scott D; Lee, Kevin; Andrews, Zane B; Bischof, Robert; Fahri, Fahri; Evans, Roger G; Clarke, Iain J; Henry, Belinda A

    2012-11-15

    This study aimed to determine whether postprandial temperature excursions in skeletal muscle are consistent with thermogenesis or altered blood flow. Temperature probes were implanted into the vastus lateralis muscle of ovariectomized ewes, and blood flow was assessed using laser-Doppler flowmetry (tissue flow) and transit-time ultrasound flowmetry (femoral artery flow). The animals were program-fed between 1100 and 1600, and temperature and blood flow were measured during intravenous administration of either isoprenaline or phenylephrine and during feeding and meal anticipation. In addition, muscle biopsies were collected prefeeding and postfeeding to measure uncoupling protein (UCP) expression and mitochondrial function, as well as indices of calcium cycling (ryanodine 1 receptor: RyR1 and sarcoendoplasmic calcium-dependent ATPases SERCA1/ SERCA2a). Isoprenaline increased femoral artery blood flow, whereas phenylephrine reduced blood flow. At high doses only, isoprenaline treatment increased heat production in muscle. Phenylephrine treatment did not alter muscle temperature. Meal anticipation was evoked in fasted animals (previously program-fed) that were housed beside animals that were fed. Increases in muscle temperature were elicited by feeding and meal anticipation, without changes in blood flow during either paradigm. Analyses of respiration in isolated mitochondria indicated that the postprandial increase in heat production was associated with an increase in state 4 respiration, without increased UCP1, UCP2, or UCP3 expression. Feeding increased the expression of RyR1 and SERCA2a. We conclude that excursions in muscle temperature may occur independent of blood flow, suggesting that postprandial heat production is driven by altered mitochondrial function and changes in calcium cycling.

  16. Daily Overfeeding from Protein and/or Carbohydrate Supplementation for Eight Weeks in Conjunction with Resistance Training Does not Improve Body Composition and Muscle Strength or Increase Markers Indicative of Muscle Protein Synthesis and Myogenesis in Resistance-Trained Males

    PubMed Central

    Spillane, Mike; Willoughby, Darryn S.

    2016-01-01

    This study determined the effects of heavy resistance training and daily overfeeding with carbohydrate and/or protein on blood and skeletal muscle markers of protein synthesis (MPS), myogenesis, body composition, and muscle performance. Twenty one resistance-trained males were randomly assigned to either a protein + carbohydrate [HPC (n = 11)] or a carbohydrate [HC (n = 10)] supplement group in a double-blind fashion. Body composition and muscle performance were assessed, and venous blood samples and muscle biopsies were obtained before and after eight weeks of resistance training and supplementation. Data were analyzed by two-way ANOVA (p ≤ 0.05). Total body mass, body water, and fat mass were significantly increased in both groups in response to resistance training, but not supplementation (p < 0.05); however, lean mass was not significantly increased in either group (p = 0.068). Upper- (p = 0.024) and lower-body (p = 0.001) muscle strength and myosin heavy chain (MHC) 1 (p = 0.039) and MHC 2A (p = 0.027) were also significantly increased with resistance training. Serum IGF-1, GH, and HGF were not significantly affected (p > 0.05). Muscle total DNA, total protein, and c-Met were not significantly affected (p > 0.05). In conjunction with resistance training, the peri-exercise and daily overfeeding of protein and/or carbohydrate did not preferentially improve body composition, muscle performance, and markers indicative of MPS and myogenic activation. Key points In response to 56 days of heavy resistance training and HC or HPC supplementation, similar increases in muscle mass and strength in both groups occurred; however, the increases were not different between supplement groups. The supplementation of HPC had no preferential effect on augmenting serum IGF-1 GH, or HGF. The supplementation of HPC had no preferential effect on augmenting increases in total muscle protein content or the myogenic markers, total DNA and muscle cMet content. In response to 56 days of

  17. Daily Overfeeding from Protein and/or Carbohydrate Supplementation for Eight Weeks in Conjunction with Resistance Training Does not Improve Body Composition and Muscle Strength or Increase Markers Indicative of Muscle Protein Synthesis and Myogenesis in Resistance-Trained Males.

    PubMed

    Spillane, Mike; Willoughby, Darryn S

    2016-03-01

    This study determined the effects of heavy resistance training and daily overfeeding with carbohydrate and/or protein on blood and skeletal muscle markers of protein synthesis (MPS), myogenesis, body composition, and muscle performance. Twenty one resistance-trained males were randomly assigned to either a protein + carbohydrate [HPC (n = 11)] or a carbohydrate [HC (n = 10)] supplement group in a double-blind fashion. Body composition and muscle performance were assessed, and venous blood samples and muscle biopsies were obtained before and after eight weeks of resistance training and supplementation. Data were analyzed by two-way ANOVA (p ≤ 0.05). Total body mass, body water, and fat mass were significantly increased in both groups in response to resistance training, but not supplementation (p < 0.05); however, lean mass was not significantly increased in either group (p = 0.068). Upper- (p = 0.024) and lower-body (p = 0.001) muscle strength and myosin heavy chain (MHC) 1 (p = 0.039) and MHC 2A (p = 0.027) were also significantly increased with resistance training. Serum IGF-1, GH, and HGF were not significantly affected (p > 0.05). Muscle total DNA, total protein, and c-Met were not significantly affected (p > 0.05). In conjunction with resistance training, the peri-exercise and daily overfeeding of protein and/or carbohydrate did not preferentially improve body composition, muscle performance, and markers indicative of MPS and myogenic activation. Key pointsIn response to 56 days of heavy resistance training and HC or HPC supplementation, similar increases in muscle mass and strength in both groups occurred; however, the increases were not different between supplement groups.The supplementation of HPC had no preferential effect on augmenting serum IGF-1 GH, or HGF.The supplementation of HPC had no preferential effect on augmenting increases in total muscle protein content or the myogenic markers, total DNA and muscle cMet content.In response to 56 days of a

  18. Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats.

    PubMed

    Khan, Haseena Banu Hedayathullah; Shanmugavalli, R; Rajendran, Deepa; Bai, Mookambikai Ramya; Sorimuthu, Subramanian

    2013-12-01

    Psidium guajava is an important plant of high medicinal value and has been used in traditional systems of medicine against various ailments. The antidiabetic effect of the ethanolic extract of Psidium guajava leaves and also its protective effect on altered glucose metabolism was evaluated in streptozotocin (stz)-induced diabetic rat model. Diabetes was induced in rats by means of intraperitoneal injection of 50-mg/kg body weight (b.wt.) of stz. Diabetes-induced rats were randomly divided into two groups. One group of rats was treated with Psidium guajava leaf extract at a dosage of 300-mg/kg b.wt. and the other group of rats was treated with the standard drug glyclazide at a dosage of 5-mg/kg b.wt. for 30 days. The blood glucose levels, plasma insulin, Hb, HbA1c were measured. The effect on the drug on altered glucose metabolizing enzymes were also studied. Treatment with Psidium guajava extract showed a significant reduction in blood glucose and HbA1c levels and a significant increase in plasma insulin levels. The drug also significantly restored the activities of carbohydrate metabolizing enzymes. This suggests that the potential antidiabetic effect of the ethanolic extract of the Psidium guajava leaves may be due to the presence of flavonoids and other phenolic components present in the drug.

  19. Length-tension relationships are altered in regenerating muscles of the rat after bupivacaine injection.

    PubMed

    Plant, David R; Beitzel, Felice; Lynch, Gordon S

    2005-06-01

    Intramuscular injection of bupivacaine causes complete degeneration of fibers in extensor digitorum longus (EDL) muscles of rats, followed by complete regeneration within 60 days. Previous studies have shown that regenerated EDL muscles are protected from contraction-induced injury 60 days after bupivacaine injection. It is possible that these regenerated muscles have altered length-tension relations because of fiber remodeling. We tested the hypothesis that length-tension relations are different in bupivacaine-injected and noninjected control muscles. EDL and soleus muscles of the right hindlimb of deeply anesthetized rats were injected with bupivacaine and then allowed to recover for 7, 14, 21, or 60 days (7D, 14D, 21D, 60D), and isometric contractile properties were assessed. Muscles of the contralateral limb were not injected and served as control. EDL muscles recovered from bupivacaine injection more rapidly than soleus muscles, with mass restored to control levels at 21D, and isometric tetanic force (P(o)) restored to control at 60D. In contrast, mass and P(o) of injected soleus muscles was not restored to control even at 60D. In 7D EDL muscles, length-tension curves were shifted leftward compared with control, but in 21D and 60D EDL muscles length-tension curves were right shifted significantly (treatment x muscle length: P < 0.001). Although no clear shift in the position of the length-tension curve was observed in regenerating soleus muscles, force production was enhanced on the descending limb of the curve in 60D soleus muscles (treatment x relative muscle length: P < 0.01). The rightward shift in the length-tension curve of EDL muscles 60 days after bupivacaine injection is likely to contribute to the mechanism for their previously observed protection from contraction-induced injury.

  20. Direction-Dependent Phasing of Locomotor Muscle Activity Is Altered Post-Stroke

    PubMed Central

    Schindler-Ivens, Sheila; Brown, David A.; Brooke, John D.

    2014-01-01

    A major contributor to impaired locomotion post-stroke is abnormal phasing of muscle activity. While inappropriate paretic muscle phasing adapts to changing body orientation, load, and speed, it remains unclear whether paretic muscle phasing adapts to reversal of locomotor direction. We examined muscle phasing in backward pedaling, a task that requires shifts in biarticular but not uniarticular muscle phasing relative to forward pedaling. We hypothesized that if paretic and neurologically intact muscle phasing adapt similarly, then paretic biarticular but not paretic uniarticular muscles would shift phasing in backward pedaling. Paretic and neurologically intact individuals pedaled forward and backward while recording electromyograms (EMGs) from vastus medialis (VM), soleus (SOL), rectus femoris (RF), semimembranosus (SM), and biceps femoris (BF). Changes in muscle phasing were assessed by comparing the probability of muscle activity in forward and backward pedaling throughout 18 pedaling cycles. Paretic uniarticular muscles (VM and SOL) showed phase-advanced activity in backward versus forward pedaling, whereas the corresponding neurologically intact muscles showed little to no phasing change. Paretic biarticular muscles were less likely than neurologically intact biarticular muscles to display phasing changes in backward pedaling. Paretic RF displayed no phase change during backward pedaling, and paretic BF displayed no consistent adaptation to backward pedaling. Paretic SM was the only muscle to display backward/forward phase changes that were similar to the neurologically intact group. We conclude that paretic uniarticular muscles are more susceptible and paretic biarticular muscles are less susceptible to direction-dependent phase shifts, consistent with altered sensory integration and impaired cortical control of locomotion. PMID:15175363

  1. Winter warming delays dormancy release, advances budburst, alters carbohydrate metabolism and reduces yield in a temperate shrub

    PubMed Central

    Pagter, Majken; Andersen, Uffe Brandt; Andersen, Lillie

    2015-01-01

    Global climate models predict an increase in the mean surface air temperature, with a disproportionate increase during winter. Since temperature is a major driver of phenological events in temperate woody perennials, warming is likely to induce changes in a range of these events. We investigated the impact of slightly elevated temperatures (+0.76 °C in the air, +1.35 °C in the soil) during the non-growing season (October–April) on freezing tolerance, carbohydrate metabolism, dormancy release, spring phenology and reproductive output in two blackcurrant (Ribes nigrum) cultivars to understand how winter warming modifies phenological traits in a woody perennial known to have a large chilling requirement and to be sensitive to spring frost. Warming delayed dormancy release more in the cultivar ‘Narve Viking’ than in the cultivar ‘Titania’, but advanced budburst and flowering predominantly in ‘Titania’. Since ‘Narve Viking’ has a higher chilling requirement than ‘Titania’, this indicates that, in high-chilling-requiring genotypes, dormancy responses may temper the effect of warming on spring phenology. Winter warming significantly reduced fruit yield the following summer in both cultivars, corroborating the hypothesis that a decline in winter chill may decrease reproductive effort in blackcurrant. Elevated winter temperatures tended to decrease stem freezing tolerance during cold acclimation and deacclimation, but it did not increase the risk of freeze-induced damage mid-winter. Plants at elevated temperature showed decreased levels of sucrose in stems of both cultivars and flower buds of ‘Narve Viking’, which, in buds, was associated with increased concentrations of glucose and fructose. Hence, winter warming influences carbohydrate metabolism, but it remains to be elucidated whether decreased sucrose levels account for any changes in freezing tolerance. Our results demonstrate that even a slight increase in winter temperature may alter

  2. Winter warming delays dormancy release, advances budburst, alters carbohydrate metabolism and reduces yield in a temperate shrub.

    PubMed

    Pagter, Majken; Andersen, Uffe Brandt; Andersen, Lillie

    2015-03-23

    Global climate models predict an increase in the mean surface air temperature, with a disproportionate increase during winter. Since temperature is a major driver of phenological events in temperate woody perennials, warming is likely to induce changes in a range of these events. We investigated the impact of slightly elevated temperatures (+0.76 °C in the air, +1.35 °C in the soil) during the non-growing season (October-April) on freezing tolerance, carbohydrate metabolism, dormancy release, spring phenology and reproductive output in two blackcurrant (Ribes nigrum) cultivars to understand how winter warming modifies phenological traits in a woody perennial known to have a large chilling requirement and to be sensitive to spring frost. Warming delayed dormancy release more in the cultivar 'Narve Viking' than in the cultivar 'Titania', but advanced budburst and flowering predominantly in 'Titania'. Since 'Narve Viking' has a higher chilling requirement than 'Titania', this indicates that, in high-chilling-requiring genotypes, dormancy responses may temper the effect of warming on spring phenology. Winter warming significantly reduced fruit yield the following summer in both cultivars, corroborating the hypothesis that a decline in winter chill may decrease reproductive effort in blackcurrant. Elevated winter temperatures tended to decrease stem freezing tolerance during cold acclimation and deacclimation, but it did not increase the risk of freeze-induced damage mid-winter. Plants at elevated temperature showed decreased levels of sucrose in stems of both cultivars and flower buds of 'Narve Viking', which, in buds, was associated with increased concentrations of glucose and fructose. Hence, winter warming influences carbohydrate metabolism, but it remains to be elucidated whether decreased sucrose levels account for any changes in freezing tolerance. Our results demonstrate that even a slight increase in winter temperature may alter phenological traits in

  3. Immunologically Induced Alterations of Airway Smooth Muscle Cell Membrane

    NASA Astrophysics Data System (ADS)

    Souhrada, M.; Souhrada, J. F.

    1984-08-01

    Active and passive sensitization, both in vivo and in vitro, caused significant hyperpolarization of airway smooth muscle cell preparations isolated from guinea pigs. An increase in the contribution of the electrogenic Na+ pump to the resting membrane potential was responsible for this change. Hyperpolarization, as induced by passive sensitization, was not prevented by agents that inhibit specific mediators of anaphylaxis but was abolished when serum from sensitized animals was heated. The heat-sensitive serum factor, presumably reaginic antibodies, appears to be responsible for the membrane hyperpolarization of airway smooth muscle cells after sensitization.

  4. Metabolic alterations by indoxyl sulfate in skeletal muscle induce uremic sarcopenia in chronic kidney disease

    PubMed Central

    Sato, Emiko; Mori, Takefumi; Mishima, Eikan; Suzuki, Arisa; Sugawara, Sanae; Kurasawa, Naho; Saigusa, Daisuke; Miura, Daisuke; Morikawa-Ichinose, Tomomi; Saito, Ritsumi; Oba-Yabana, Ikuko; Oe, Yuji; Kisu, Kiyomi; Naganuma, Eri; Koizumi, Kenji; Mokudai, Takayuki; Niwano, Yoshimi; Kudo, Tai; Suzuki, Chitose; Takahashi, Nobuyuki; Sato, Hiroshi; Abe, Takaaki; Niwa, Toshimitsu; Ito, Sadayoshi

    2016-01-01

    Sarcopenia is associated with increased morbidity and mortality in chronic kidney disease (CKD). Pathogenic mechanism of skeletal muscle loss in CKD, which is defined as uremic sarcopenia, remains unclear. We found that causative pathological mechanism of uremic sarcopenia is metabolic alterations by uremic toxin indoxyl sulfate. Imaging mass spectrometry revealed indoxyl sulfate accumulated in muscle tissue of a mouse model of CKD. Comprehensive metabolomics revealed that indoxyl sulfate induces metabolic alterations such as upregulation of glycolysis, including pentose phosphate pathway acceleration as antioxidative stress response, via nuclear factor (erythroid-2-related factor)-2. The altered metabolic flow to excess antioxidative response resulted in downregulation of TCA cycle and its effected mitochondrial dysfunction and ATP shortage in muscle cells. In clinical research, a significant inverse association between plasma indoxyl sulfate and skeletal muscle mass in CKD patients was observed. Our results indicate that indoxyl sulfate is a pathogenic factor for sarcopenia in CKD. PMID:27830716

  5. Addition of Carbohydrate or Alanine to an Essential Amino Acid Mixture Does Not Enhance Human Skeletal Muscle Protein Anabolism123

    PubMed Central

    Glynn, Erin L.; Fry, Christopher S.; Timmerman, Kyle L.; Drummond, Micah J.; Volpi, Elena; Rasmussen, Blake B.

    2013-01-01

    In humans, essential amino acids (EAAs) stimulate muscle protein synthesis (MPS) with no effect on muscle protein breakdown (MPB). Insulin can stimulate MPS, and carbohydrates (CHOs) and insulin decrease MPB. Net protein balance (NB; indicator of overall anabolism) is greatest when MPS is maximized and MPB is minimized. To determine whether adding CHO or a gluconeogenic amino acid to EAAs would improve NB compared with EAA alone, young men and women (n = 21) ingested 10 g EAA alone, with 30 g sucrose (EAA+CHO), or with 30 g alanine (EAA+ALA). The fractional synthetic rate and phenylalanine kinetics (MPS, MPB, NB) were assessed by stable isotopic methods on muscle biopsies at baseline and 60 and 180 min following nutrient ingestion. Insulin increased 30 min postingestion in all groups and remained elevated in the EAA+CHO and EAA+ALA groups for 60 and 120 min, respectively. The fractional synthetic rate increased from baseline at 60 min in all groups (P < 0.05; EAA = 0.053 ± 0.018 to 0.090 ± 0.039% · h−1; EAA+ALA = 0.051 ± 0.005 to 0.087 ± 0.015% · h−1; EAA+CHO = 0.049 ± 0.006 to 0.115 ± 0.024% · h−1). MPS and NB peaked at 30 min in the EAA and EAA+CHO groups but at 60 min in the EAA+ALA group and NB was elevated above baseline longer in the EAA+ALA group than in the EAA group (P < 0.05). Although responses were more robust in the EAA+CHO group and prolonged in the EAA+ALA group, AUCs were similar among all groups for fractional synthetic rate, MPS, MPB, and NB. Because the overall muscle protein anabolic response was not improved in either the EAA+ALA or EAA+CHO group compared with EAA, we conclude that protein nutritional interventions to enhance muscle protein anabolism do not require such additional energy. PMID:23343676

  6. Collagen content does not alter the passive mechanical properties of fibrotic skeletal muscle in mdx mice

    PubMed Central

    Smith, Lucas R.

    2014-01-01

    Many skeletal muscle diseases are associated with progressive fibrosis leading to impaired muscle function. Collagen within the extracellular matrix is the primary structural protein providing a mechanical scaffold for cells within tissues. During fibrosis collagen not only increases in amount but also undergoes posttranslational changes that alter its organization that is thought to contribute to tissue stiffness. Little, however, is known about collagen organization in fibrotic muscle and its consequences for function. To investigate the relationship between collagen content and organization with muscle mechanical properties, we studied mdx mice, a model for Duchenne muscular dystrophy (DMD) that undergoes skeletal muscle fibrosis, and age-matched control mice. We determined collagen content both histologically, with picosirius red staining, and biochemically, with hydroxyproline quantification. Collagen content increased in the mdx soleus and diaphragm muscles, which was exacerbated by age in the diaphragm. Collagen packing density, a parameter of collagen organization, was determined using circularly polarized light microscopy of picosirius red-stained sections. Extensor digitorum longus (EDL) and soleus muscle had proportionally less dense collagen in mdx muscle, while the diaphragm did not change packing density. The mdx muscles had compromised strength as expected, yet only the EDL had a significantly increased elastic stiffness. The EDL and diaphragm had increased dynamic stiffness and a change in relative viscosity. Unexpectedly, passive stiffness did not correlate with collagen content and only weakly correlated with collagen organization. We conclude that muscle fibrosis does not lead to increased passive stiffness and that collagen content is not predictive of muscle stiffness. PMID:24598364

  7. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)

    1990-01-01

    To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

  8. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)

    1990-01-01

    To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

  9. Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome.

    PubMed

    Fulle, S; Mecocci, P; Fanó, G; Vecchiet, I; Vecchini, A; Racciotti, D; Cherubini, A; Pizzigallo, E; Vecchiet, L; Senin, U; Beal, M F

    2000-12-15

    Chronic fatigue syndrome (CFS) is a poorly understood disease characterized by mental and physical fatigue, most often observed in young white females. Muscle pain at rest, exacerbated by exercise, is a common symptom. Although a specific defect in muscle metabolism has not been clearly defined, yet several studies report altered oxidative metabolism. In this study, we detected oxidative damage to DNA and lipids in muscle specimens of CFS patients as compared to age-matched controls, as well as increased activity of the antioxidant enzymes catalase, glutathione peroxidase, and transferase, and increases in total glutathione plasma levels. From these results we hypothesize that in CFS there is oxidative stress in muscle, which results in an increase in antioxidant defenses. Furthermore, in muscle membranes, fluidity and fatty acid composition are significantly different in specimens from CFS patients as compared to controls and to patients suffering from fibromyalgia. These data support an organic origin of CFS, in which muscle suffers oxidative damage.

  10. Group size modifies the patterns and muscle carbohydrate effects of aggression in Betta splendens.

    PubMed

    Haller, J

    1992-08-01

    Aggressive encounters of previously isolated individuals were investigated in dyads and groups of five. Fights were longer and more intense when they were performed in dyads compared to fights involving five fishes. During aggressive encounters, an elevation in carbohydrate catabolism was noticed in both dyads and groups. Losing a fight resulted in a reduction in glycogen content and an increase in glycogen synthesis. Similar changes in winners did not appear; thus, the metabolic response in losers was different from that noticed in winners, both in dyads and groups. In dyadic contest winners, a marked increase in the free glucose content and glucose consumption was noticed (without changes in losers). In groups, free glucose content of the winners was not modified, while glucose consumption was enhanced both in winners and losers. Thus, the differences existing between winners and losers were greater in dyads compared to those noticed in groups. The energy cost of aggression seems to be different in dyads compared to groups of five. The rate of glucose oxidation was strongly reduced in dyads (there were no differences between winners and losers in this respect), while in groups, this parameter was not modified.

  11. Altered signaling for mitochondrial and myofibrillar biogenesis in skeletal muscles of patients with multiple sclerosis.

    PubMed

    Hansen, Dominique; Wens, Inez; Vandenabeele, Frank; Verboven, Kenneth; Eijnde, Bert O

    2015-07-01

    Patients with multiple sclerosis (pwMS) experience muscle weakness and lowered muscle oxidative capacity. To explore the etiology for the development of such muscle phenotype we studied skeletal muscle adenosine monophosphate (AMP)-activated protein kinase phosphorylation (phospho-AMPKα, governing mitochondrial biogenesis) and mammalian target of rapamycin phosphorylation (phospho-mTOR, governing myofibrillar biogenesis) in pwMS. After assessment of body composition, muscle strength, exercise tolerance, and muscle fiber type, muscle phospho-AMPKα and phospho-mTOR were assessed in 14 pwMS and 10 healthy controls (part 1). Next, an endurance exercise bout was executed by 9 pwMS and 7 healthy subjects, with assessment of changes in muscle phospho-AMPKα and phospho-mTOR (part 2). Increased basal muscle phospho-AMPKα and phospho-mTOR were present in MS (P < 0.01) and independently related to MS. Correlations between muscle phospho-AMPKα or phospho-mTOR and whole-body fat mass, peak oxygen uptake, and expanded disability status scale (P < 0.05) were found. After endurance exercise muscle phospho-AMPKα and phospho-mTOR remained increased in pwMS (P < 0.01). Muscle signaling cascades for mitochondrial and myofibrillar biogenesis are altered in MS and related to the impairment and disability level. These findings indicate a link between muscle signaling cascades and the level of disability and impairment, and thus may open a new area for the development of novel therapies for peripheral muscle impairment in MS. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. [Markers for early detection of alterations in carbohydrate metabolism after acute myocardial infarction].

    PubMed

    de Gea-García, J H; Benali, L; Galcerá-Tomás, J; Padilla-Serrano, A; Andreu-Soler, E; Melgarejo-Moreno, A; Alonso-Fernández, N

    2014-03-01

    Undiagnosed abnormal glucose metabolism is often seen in patients admitted with acute myocardial infarction, although there is no consensus on which patients should be studied with a view to establishing an early diagnosis. The present study examines the potential of certain variables obtained upon admission to diagnose abnormal glucose metabolism. A prospective cohort study was carried out. The Intensive Care Unit of Arrixaca University Hospital (Murcia), Spain. A total of 138 patients admitted to the Intensive Care Unit with acute myocardial infarction and without known or de novo diabetes mellitus. After one year, oral glucose tolerance testing was performed. Clinical and laboratory test parameters were recorded upon admission and one year after discharge. Additionally, after one year, oral glucose tolerance tests were made, and a study was made of the capacity of the variables obtained at admission to diagnose diabetes, based on the ROC curves and multivariate analysis. Of the 138 patients, 112 (72.5%) had glucose metabolic alteration, including 16.7% with diabetes. HbA1c was independently associated with a diagnosis of diabetes (RR: 7.28, 95%CI 1.65 to 32.05, P = .009), and showed the largest area under the ROC curve for diabetes (0.81, 95%CI 0.69 to 0.92, P = .001). In patients with acute myocardial infarction, HbA1c helps identify those individuals with abnormal glucose metabolism after one year. Thus, its determination in this group of patients could be used to identify those subjects requiring a more exhaustive study in order to establish an early diagnosis. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  13. Altered lower leg muscle activation patterns in patients with cerebral palsy during cycling on an ergometer

    PubMed Central

    Alves-Pinto, Ana; Blumenstein, Tobias; Turova, Varvara; Lampe, Renée

    2016-01-01

    Objective Cycling on a recumbent ergometer constitutes one of the most popular rehabilitation exercises in cerebral palsy (CP). However, no control is performed on how muscles are being used during training. Given that patients with CP present altered muscular activity patterns during cycling or walking, it is possible that an incorrect pattern of muscle activation is being promoted during rehabilitation cycling. This study investigated patterns of muscular activation during cycling on a recumbent ergometer in patients with CP and whether those patterns are determined by the degree of spasticity and of mobility. Methods Electromyographic (EMG) recordings of lower leg muscle activation during cycling on a recumbent ergometer were performed in 14 adult patients diagnosed with CP and five adult healthy participants. EMG recordings were done with an eight-channel EMG system built in the laboratory. The activity of the following muscles was recorded: Musculus rectus femoris, Musculus biceps femoris, Musculus tibialis anterior, and Musculus gastrocnemius. The degree of muscle spasticity and mobility was assessed using the Modified Ashworth Scale and the Gross Motor Function Classification System, respectively. Muscle activation patterns were described in terms of onset and duration of activation as well as duration of cocontractions. Results Muscle activation in CP was characterized by earlier onsets, longer periods of activation, a higher occurrence of agonist–antagonist cocontractions, and a more variable cycling tempo in comparison to healthy participants. The degree of altered muscle activation pattern correlated significantly with the degree of spasticity. Conclusion This study confirmed the occurrence of altered lower leg muscle activation patterns in patients with CP during cycling on a recumbent ergometer. There is a need to develop feedback systems that can inform patients and therapists of an incorrect muscle activation during cycling and support the training

  14. Altered viscoelastic properties of stroke-affected muscles estimated using ultrasound shear waves - Preliminary data.

    PubMed

    Rasool, Ghulam; Wang, Allison B; Rymer, William Z; Lee, Sabrina S M

    2016-08-01

    As a result of a brain injury such as stroke, the skeletal muscles may undergo numerous structural and functional alterations. These abnormal changes are linked to muscle weakness, joint contracture, and abnormal muscle tone and eventually, result in motor impairment. A subset of these alterations affects passive muscle stiffness, i.e., viscoelastic properties. However, in vivo estimation of changes in viscoelastic properties is a challenging task. Here, we used the shear wave velocity, estimated through ultrasound SuperSonic imaging (SSI), as a surrogate for viscoelastic properties. We estimated shear wave group and phase velocities (dispersion), and thus, quantified both elasticity and viscosity of the muscle tissue, respectively in muscles of hemiplegic stroke survivors. In these individuals, we found significantly higher group and phase velocities in the stroke-affected muscles (p<; 05) compared to those of the contralateral non-affected side. We hypothesize that in addition to changes in neural and contractile properties, there are also, changes in elastic and tissue dispersive properties through local mechanisms. An enhanced understanding of post-stroke changes in skeletal muscles will lead to better and targeted interventions for rehabilitation.

  15. Altered muscle coordination when pedaling with independent cranks

    PubMed Central

    Hug, François; Boumier, Florian; Dorel, Sylvain

    2013-01-01

    Pedaling with independent cranks ensures each leg cycles independently of the other, and thus eliminates the contribution of the contralateral leg during the upstroke phase. Consequently the subject is required to actively pull-up the pedal to complete the cycle. The present study aimed to determine the acute effect of the use of independent cranks on muscle coordination during a submaximal pedaling exercise. Ten healthy males were asked to perform submaximal pedaling exercises at 100 Watts with normal fixed cranks (control condition) or independent cranks. Both 2-D pedal forces and electromyographic (EMG) SIGNALS of 10 lower limb muscles were recorded. When the mean EMG activity across the cycle was considered, the use of independent cranks significantly increased the activity level compared to control for Tibialis anterior (TA) (P = 0.0017; +336 ± 302%), Gastrocnemius medialis (GM) (P = 0.0005; +47 ± 25%), Rectus femoris (RF) (P = 0.005; +123 ± 153%), Biceps femoris (BF)—long head (P = 0.0001; +162 ± 97%), Semimembranosus (SM) (P = 0.0001; +304 ± 192%), and Tensor fascia latae (P = 0.0001; +586 ± 262%). The analysis of the four pedaling sectors revealed that the increased activity of hip and knee flexors mainly occurred during the top dead center and the upstroke phase. In addition, a high inter-individual variability was found in the way the participants adapted to pedaling with independent cranks. The present results showed that the enforced pull-up action required when using independent cranks was achieved by increasing the activation of hip and knee flexors. Further studies are needed to determine whether training with independent cranks has the potential to induce long-term changes in muscle coordination, and, if so, whether these changes are beneficial for cycling performance. PMID:24009587

  16. Altered muscle coordination when pedaling with independent cranks.

    PubMed

    Hug, François; Boumier, Florian; Dorel, Sylvain

    2013-01-01

    Pedaling with independent cranks ensures each leg cycles independently of the other, and thus eliminates the contribution of the contralateral leg during the upstroke phase. Consequently the subject is required to actively pull-up the pedal to complete the cycle. The present study aimed to determine the acute effect of the use of independent cranks on muscle coordination during a submaximal pedaling exercise. Ten healthy males were asked to perform submaximal pedaling exercises at 100 Watts with normal fixed cranks (control condition) or independent cranks. Both 2-D pedal forces and electromyographic (EMG) SIGNALS of 10 lower limb muscles were recorded. When the mean EMG activity across the cycle was considered, the use of independent cranks significantly increased the activity level compared to control for Tibialis anterior (TA) (P = 0.0017; +336 ± 302%), Gastrocnemius medialis (GM) (P = 0.0005; +47 ± 25%), Rectus femoris (RF) (P = 0.005; +123 ± 153%), Biceps femoris (BF)-long head (P = 0.0001; +162 ± 97%), Semimembranosus (SM) (P = 0.0001; +304 ± 192%), and Tensor fascia latae (P = 0.0001; +586 ± 262%). The analysis of the four pedaling sectors revealed that the increased activity of hip and knee flexors mainly occurred during the top dead center and the upstroke phase. In addition, a high inter-individual variability was found in the way the participants adapted to pedaling with independent cranks. The present results showed that the enforced pull-up action required when using independent cranks was achieved by increasing the activation of hip and knee flexors. Further studies are needed to determine whether training with independent cranks has the potential to induce long-term changes in muscle coordination, and, if so, whether these changes are beneficial for cycling performance.

  17. Altered Muscle Metabolism in Rats After Thermal Injury

    DTIC Science & Technology

    1982-12-01

    by Herndon et a-ketoglutarate. 600 mM L -alanine, 0.18 mM NADH. 1.2 U/ml al." Briefly, this procedure consists of anesthetizing the rat (50 mg lactate...whole homogenates of the gastrocnemius muscle 9 sec and the abdomen for 3 sec in 980C water. Saline (20 ml) was to oxidize pyruvate- l -"C to "CO, was...the same time Econofluor (New England Nuclear, Boston. Mass.) and 10% metha- of day. nol. Oleate- l -’C oxidation rates by whole gastrocnemius homoge

  18. High temperature limits in vivo pollen tube growth rates by altering diurnal carbohydrate balance in field-grown Gossypium hirsutum pistils.

    PubMed

    Snider, John L; Oosterhuis, Derrick M; Loka, Dimitra A; Kawakami, Eduardo M

    2011-07-15

    It has recently been reported that high temperature slows in vivo pollen tube growth rates in Gossypium hirsutum pistils under field conditions. Although numerous physical and biochemical pollen-pistil interactions are necessary for in vivo pollen tube growth to occur, studies investigating the influence of heat-induced changes in pistil biochemistry on in vivo pollen tube growth rates are lacking. We hypothesized that high temperature would alter diurnal pistil biochemistry and that pollen tube growth rates would be dependent upon the soluble carbohydrate content of the pistil during pollen tube growth. G. hirsutum seeds were sown on different dates to obtain flowers exposed to contrasting ambient temperatures but at the same developmental stage. Diurnal pistil measurements included carbohydrate balance, glutathione reductase (GR; EC 1.8.1.7), soluble protein, superoxide dismutase (SOD; EC 1.15.1.1), NADPH oxidase (NOX; EC 1.6.3.1), adenosine triphosphate (ATP), and water-soluble calcium. Soluble carbohydrate levels in cotton pistils were as much as 67.5% lower under high temperature conditions (34.6 °C maximum air temperature; August 4, 2009) than under cooler conditions (29.9 °C maximum air temperature; August 14, 2009). Regression analysis revealed that pollen tube growth rates were highly correlated with the soluble carbohydrate content of the pistil during pollen tube growth (r² = 0.932). Higher ambient temperature conditions on August 4 increased GR activity in the pistil only during periods not associated with in vivo pollen tube growth; pistil protein content declined earlier in the day under high temperatures; SOD and NOX were unaffected by either sample date or time of day; pistil ATP and water soluble calcium were unaffected by the warmer temperatures. We conclude that moderate heat stress significantly alters diurnal carbohydrate balance in the pistil and suggest that pollen tube growth rate through the style may be limited by soluble carbohydrate

  19. Skeletal muscle plasticity: cellular and molecular responses to altered physical activity paradigms

    NASA Technical Reports Server (NTRS)

    Baldwin, Kenneth M.; Haddad, Fadia

    2002-01-01

    The goal of this article is to examine our current understanding of the chain of events known to be involved in the adaptive process whereby specific genes and their protein products undergo altered expression; specifically, skeletal muscle adaptation in response to altered loading states will be discussed, with a special focus on the regulation of the contractile protein, myosin heavy chain gene expression. This protein, which is both an important structural and regulatory protein comprising the contractile apparatus, can be expressed as different isoforms, thereby having an impact on the functional diversity of the muscle. Because the regulation of the myosin gene family is under the control of a complex set of processes including, but not limited to, activity, hormonal, and metabolic factors, this protein will serve as a cellular "marker" for studies of muscle plasticity in response to various mechanical perturbations in which the quantity and type of myosin isoform, along with other important cellular proteins, are altered in expression.

  20. Skeletal muscle plasticity: cellular and molecular responses to altered physical activity paradigms

    NASA Technical Reports Server (NTRS)

    Baldwin, Kenneth M.; Haddad, Fadia

    2002-01-01

    The goal of this article is to examine our current understanding of the chain of events known to be involved in the adaptive process whereby specific genes and their protein products undergo altered expression; specifically, skeletal muscle adaptation in response to altered loading states will be discussed, with a special focus on the regulation of the contractile protein, myosin heavy chain gene expression. This protein, which is both an important structural and regulatory protein comprising the contractile apparatus, can be expressed as different isoforms, thereby having an impact on the functional diversity of the muscle. Because the regulation of the myosin gene family is under the control of a complex set of processes including, but not limited to, activity, hormonal, and metabolic factors, this protein will serve as a cellular "marker" for studies of muscle plasticity in response to various mechanical perturbations in which the quantity and type of myosin isoform, along with other important cellular proteins, are altered in expression.

  1. Skeletal muscle plasticity: cellular and molecular responses to altered physical activity paradigms.

    PubMed

    Baldwin, Kenneth M; Haddad, Fadia

    2002-11-01

    The goal of this article is to examine our current understanding of the chain of events known to be involved in the adaptive process whereby specific genes and their protein products undergo altered expression; specifically, skeletal muscle adaptation in response to altered loading states will be discussed, with a special focus on the regulation of the contractile protein, myosin heavy chain gene expression. This protein, which is both an important structural and regulatory protein comprising the contractile apparatus, can be expressed as different isoforms, thereby having an impact on the functional diversity of the muscle. Because the regulation of the myosin gene family is under the control of a complex set of processes including, but not limited to, activity, hormonal, and metabolic factors, this protein will serve as a cellular "marker" for studies of muscle plasticity in response to various mechanical perturbations in which the quantity and type of myosin isoform, along with other important cellular proteins, are altered in expression.

  2. Metabolic alterations induced in cultured skeletal muscle by stretch-relaxation activity

    NASA Technical Reports Server (NTRS)

    Hatfaludy, Sophia; Shansky, Janet; Vandenburgh, Herman H.

    1989-01-01

    Muscle cells differentiated in vitro are repetitively stretched and relaxed in order to determine the presence of short- and long-term alterations occurring in glucose uptake and lactate efflux that are similar to the metabolic alterations occurring in stimulated organ-cultured muscle and in vivo skeletal muscle during the active state. It is observed that whereas mechanical stimulation increases these metabolic parameters within 4-6 h of starting activity, unstimulated basal rates in control cultures also increase during this period of time, and by 8 h, their rates have reached or exceeded the rates in continuously stimulated cells. Measurements of these parameters in media of different compositions show that activity-induced long-term alterations in the parameters occur independently of growth factors in serium and embryo extracts.

  3. Metabolic alterations induced in cultured skeletal muscle by stretch-relaxation activity

    NASA Technical Reports Server (NTRS)

    Hatfaludy, Sophia; Shansky, Janet; Vandenburgh, Herman H.

    1989-01-01

    Muscle cells differentiated in vitro are repetitively stretched and relaxed in order to determine the presence of short- and long-term alterations occurring in glucose uptake and lactate efflux that are similar to the metabolic alterations occurring in stimulated organ-cultured muscle and in vivo skeletal muscle during the active state. It is observed that whereas mechanical stimulation increases these metabolic parameters within 4-6 h of starting activity, unstimulated basal rates in control cultures also increase during this period of time, and by 8 h, their rates have reached or exceeded the rates in continuously stimulated cells. Measurements of these parameters in media of different compositions show that activity-induced long-term alterations in the parameters occur independently of growth factors in serium and embryo extracts.

  4. Adding Fish Oil to Whey Protein, Leucine and Carbohydrate Over a 6 Week Supplementation Period Attenuates Muscle Soreness Following Eccentric Exercise in Competitive Soccer Players.

    PubMed

    Philpott, Jordan D; Donnelly, Chris; Walshe, Ian H; Dick, James; Galloway, Stuart D R; Tipton, Kevin D; Witard, Oliver C

    2017-09-05

    Soccer players often experience eccentric exercise-induced muscle damage given the physical demands of soccer match-play. Since long chain n-3 polyunsaturated fatty acids (n-3PUFA) enhance muscle sensitivity to protein supplementation, dietary supplementation with a combination of fish oil-derived n-3PUFA, protein and carbohydrate may promote exercise recovery. This study examined the influence of adding n-3PUFA to a whey protein, leucine and carbohydrate containing beverage over a 6 week supplementation period on physiological markers of recovery measured over 3 days following eccentric exercise. Competitive soccer players were assigned to one of three conditions (2 × 200mL): FO (n=10) contained n-3PUFA (1100mg DHA/EPA - approx. 550mg DHA, 550mg EPA), whey protein (15g), leucine (1.8g) and carbohydrate (20g); PRO (n=10) contained whey protein (15g), leucine (1.8g) and carbohydrate (20g) and CHO (n=10) contained carbohydrate (24g). Eccentric exercise consisted of unilateral knee extension/flexion contractions on both legs separately. Maximal force production was impaired by 22% during the 72 hour recovery period following eccentric exercise (p<0.05). Muscle soreness, expressed as AUC during 72 hour recovery, was less in FO (1948±1091 mm×72 h) than PRO (4640±2654 mm×72h, p<0.05) and CHO (4495±1853 mm×72h p=0.10). Blood concentrations of creatine kinase, expressed as AUC, were ~60% lower in FO compared to CHO (p<0.05) and tended to be lower (~39%, p = 0.07) than PRO. No differences in muscle function, soccer performance or blood c-reactive protein concentrations were observed between groups. In conclusion, the addition of n-3PUFA to a beverage containing whey protein, leucine and carbohydrate ameliorates the increase in muscle soreness and blood concentrations of creatine kinase following eccentric exercise in competitive soccer players.

  5. Characterizing the glycocalyx of poultry spermatozoa: III. Semen cryopreservation methods alter the carbohydrate component of rooster sperm membrane glycoconjugates.

    PubMed

    Peláez, J; Bongalhardo, D C; Long, J A

    2011-02-01

    The carbohydrate-rich zone on the sperm surface is essential for inmunoprotection in the female tract and early gamete interactions. We recently have shown the glycocalyx of chicken sperm to be extensively sialylated and to contain residues of mannose, glucose, galactose, fucose, N-acetyl-galactosamine, N-acetyl-glucosamine, and N-acetyl-lactosamine. Our objective here was to evaluate the effects of 3 different cryopreservation methods on the sperm glycocalyx. Semen from roosters was pooled, diluted, cooled to 5°C, and aliquoted for cryopreservation using 6% dimethylacetamide (DMA), 11% dimethylsulfoxide (DMSO), or 11% glycerol (GOH). For the DMA method, semen was equilibrated for 1 min with cryoprotectant and rapidly frozen by dropping 25-µL aliquots into liquid nitrogen. For the other methods, semen was equilibrated for either 1 min (DMSO) or 20 min (GOH), loaded into straws, and frozen with a programmable freezer. Thawing rates mimicked the freezing rates (e.g., rapid for DMA; moderate for DMSO and GOH). Aliquots of thawed and fresh, unfrozen semen were incubated with 1 of 12 fluorescein isothiocyanate-conjugated lectins and counterstained with propidium iodide, and mean fluorescence intensity (MFI) was assessed by flow cytometry. For each lectin, the MFI of propidium iodide-negative (viable sperm) was compared among the fresh and frozen-thawed treatments (n = 5). For sperm frozen with GOH and DMA, the MFI of most lectins was similar (P > 0.05) to that of fresh sperm, whereas only 5 of 12 lectins were similar between fresh and DMSO-frozen sperm. Sperm from all 3 methods had higher (P < 0.05) MFI for lectins specific for N-acetyl-glucosamine and β-galactose than did fresh sperm. Fewer sperm were damaged (P < 0.001) with GOH than with DMA or DMSO, and membrane integrity was correlated with MFI for 9 of 12 lectins (P < 0.05). These data indicate that surface carbohydrates are altered during cryopreservation, and that cryoprotectant type and freezing

  6. Changes in timing of muscle contractions and running economy with altered stride pattern during running.

    PubMed

    Connick, Mark J; Li, Francois-Xavier

    2014-01-01

    Large alterations to the preferred running stride decrease running economy, and shorter strides increase leg muscle activity. However, the effect of altered strides on the timing of leg muscle activation is not known. The aim of this study was to evaluate the impact of moderate alterations to the running stride on running economy and the timing of biceps femoris (BF), vastus lateralis (VL) and gastrocnemius (GAST) muscle contractions. The preferred stride pattern for eleven trained male runners was measured prior to a separate visit where participants ran for bouts of 5 min whilst synchronising foot contacts to a metronome signal which was tuned to (1) the preferred stride, and (2) frequencies which related to ± 8% and ± 4% of the preferred stride length. Running economy was measured at each stride pattern along with electromyography and three-dimensional kinematics to estimate onset and offset of muscle contractions for each muscle. Running economy was greatest at the preferred stride length. However, a quadratic fit to the data was optimised at a stride which was 2.9% shorter than preferred. Onset and offset of BF and VL muscle contractions occurred earlier with shorter than preferred strides. We detected no changes to the timing of muscle contractions with longer than preferred strides and no changes to GAST muscle contractions. The results suggest that runners optimise running economy with a stride length that is close to, but shorter than, the preferred stride, and that timing of BF and VL muscle contractions change with shorter than preferred strides. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Muscle fluid shift does not alter EMG global variables during sustained isometric actions.

    PubMed

    von Walden, Ferdinand; Pozzo, Marco; Elman, Ted; Tesch, Per A

    2008-10-01

    Body fluid redistribution occurs in astronauts traveling in space, potentially altering interstitial water content and hence impedance. This in turn may impact the features of electromyographic (EMG) signals measured to compare in-flight muscle function with pre- and post-flight conditions. Thus, the current study aimed at investigating the influence of similar fluid shifts on EMG spectral variables during muscle contractile activity. Ten men performed sustained isometric actions (120 s) at 20% and 60% of maximum voluntary contraction (MVC) following 1-h rest in the vertical or supine position. From single differential EMG signals, recorded from the soleus (SOL), the medial (MG) and lateral (LG) gastrocnemius muscles, initial value and rate of change over time (slope) of mean power frequency (MNF) and average rectified value (ARV) were assessed. MNF initial value showed dependence on muscle (P<0.01), but was unaffected by body tilt. MNF rate of change increased (P<0.001) with increased force and differed across muscles (P<0.05), but was not influenced (P=0.85) by altered body position. Thus, fluid shift resulting from vertical to supine tilt had no impact on myoelectrical manifestations of muscle fatigue. Furthermore, since such alteration of body fluid distribution resembles that occurring in microgravity, our findings suggest this may not be a methodological limitation, when comparing EMG fatigue indices on Earth versus in space.

  8. Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Disease

    PubMed Central

    Chen, Neal X.; Organ, Jason M.; Zarse, Chad; O’Neill, Kalisha; Conway, Richard G.; Konrad, Robert J.; Bacallao, Robert L.; Allen, Matthew R.; Moe, Sharon M.

    2016-01-01

    Skeletal muscle atrophy and impaired muscle function are associated with lower health-related quality of life, and greater disability and mortality risk in those with chronic kidney disease (CKD). However, the pathogenesis of skeletal dysfunction in CKD is unknown. We used a slow progressing, naturally occurring, CKD rat model (Cy/+ rat) with hormonal abnormalities consistent with clinical presentations of CKD to study skeletal muscle signaling. The CKD rats demonstrated augmented skeletal muscle regeneration with higher activation and differentiation signals in muscle cells (i.e. lower Pax-7; higher MyoD and myogenin RNA expression). However, there was also higher expression of proteolytic markers (Atrogin-1 and MuRF-1) in CKD muscle relative to normal. CKD animals had higher indices of oxidative stress compared to normal, evident by elevated plasma levels of an oxidative stress marker, 8-hydroxy-2' -deoxyguanosine (8-OHdG), increased muscle expression of succinate dehydrogenase (SDH) and Nox4 and altered mitochondria morphology. Furthermore, we show significantly higher serum levels of myostatin and expression of myostatin in skeletal muscle of CKD animals compared to normal. Taken together, these data show aberrant regeneration and proteolytic signaling that is associated with oxidative stress and high levels of myostatin in the setting of CKD. These changes likely play a role in the compromised skeletal muscle function that exists in CKD. PMID:27486747

  9. Alcohol consumption and hormonal alterations related to muscle hypertrophy: a review

    PubMed Central

    2014-01-01

    Detrimental effects of acute and chronic alcohol (ethanol) consumption on human physiology are well documented in the literature. These adversely influence neural, metabolic, cardiovascular, and thermoregulatory functions. However, the side effects of ethanol consumption on hormonal fluctuations and subsequent related skeletal muscle alterations have received less attention and as such are not entirely understood. The focus of this review is to identify the side effects of ethanol consumption on the major hormones related to muscle metabolism and clarify how the hormonal profiles are altered by such consumption. PMID:24932207

  10. Systemic response to thermal injury in rats. Accelerated protein degradation and altered glucose utilization in muscle.

    PubMed Central

    Clark, A S; Kelly, R A; Mitch, W E

    1984-01-01

    Negative nitrogen balance and increased oxygen consumption after thermal injury in humans and experimental animals is related to the extent of the burn. To determine whether defective muscle metabolism is restricted to the region of injury, we studied protein and glucose metabolism in forelimb muscles of rats 48 h after a scalding injury of their hindquarters. This injury increased muscle protein degradation (PD) from 140 +/- 5 to 225 +/- 5 nmol tyrosine/g per h, but did not alter protein synthesis. Muscle lactate release was increased greater than 70%, even though plasma catecholamines and muscle cyclic AMP were not increased. Insulin dose-response studies revealed that the burn decreased the responsiveness of muscle glycogen synthesis to insulin but did not alter its sensitivity to insulin. Rates of net glycolysis and glucose oxidation were increased and substrate cycling of fructose-6-phosphate was decreased at all levels of insulin. The burn-induced increase in protein and glucose catabolism was not mediated by adrenal hormones, since they persisted despite adrenalectomy. Muscle PGE2 production was not increased by the burn and inhibition of prostaglandin synthesis by indomethacin did not inhibit proteolysis. The increase in PD required lysosomal proteolysis, since inhibition of cathepsin B with EP475 reduced PD. Insulin reduced PD 20% and the effects of EP475 and insulin were additive, reducing PD 41%. An inhibitor of muscle PD, alpha-ketoisocaproate, reduced burn-induced proteolysis 28% and lactate release 56%. The rate of PD in muscle of burned and unburned rats was correlated with the percentage of glucose uptake that was directed into lactate production (r = +0.82, P less than 0.01). Thus, a major thermal injury causes hypercatabolism of protein and glucose in muscle that is distant from the injury, and these responses may be linked to a single metabolic defect. PMID:6470144

  11. Altered Protein Composition and Gene Expression in Strabismic Human Extraocular Muscles and Tendons

    PubMed Central

    Agarwal, Andrea B.; Feng, Cheng-Yuan; Altick, Amy L.; Quilici, David R.; Wen, Dan; Johnson, L. Alan; von Bartheld, Christopher S.

    2016-01-01

    Purpose To determine whether structural protein composition and expression of key regulatory genes are altered in strabismic human extraocular muscles. Methods Samples from strabismic horizontal extraocular muscles were obtained during strabismus surgery and compared with normal muscles from organ donors. We used proteomics, standard and customized PCR arrays, and microarrays to identify changes in major structural proteins and changes in gene expression. We focused on muscle and connective tissue and its control by enzymes, growth factors, and cytokines. Results Strabismic muscles showed downregulation of myosins, tropomyosins, troponins, and titin. Expression of collagens and regulators of collagen synthesis and degradation, the collagenase matrix metalloproteinase (MMP)2 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)1 and TIMP2, was upregulated, along with tumor necrosis factor (TNF), TNF receptors, and connective tissue growth factor (CTGF), as well as proteoglycans. Growth factors controlling extracellular matrix (ECM) were also upregulated. Among 410 signaling genes examined by PCR arrays, molecules with downregulation in the strabismic phenotype included GDNF, NRG1, and PAX7; CTGF, CXCR4, NPY1R, TNF, NTRK1, and NTRK2 were upregulated. Signaling molecules known to control extraocular muscle plasticity were predominantly expressed in the tendon rather than the muscle component. The two horizontal muscles, medial and lateral rectus, displayed similar changes in protein and gene expression, and no obvious effect of age. Conclusions Quantification of proteins and gene expression showed significant differences in the composition of extraocular muscles of strabismic patients with respect to important motor proteins, elements of the ECM, and connective tissue. Therefore, our study supports the emerging view that the molecular composition of strabismic muscles is substantially altered. PMID:27768799

  12. Central somatosensory changes and altered muscle synergies in subjects with anterior cruciate ligament deficiency.

    PubMed

    Courtney, Carol; Rine, Rose Marie; Kroll, Penny

    2005-08-01

    To clarify the mechanisms of compensation in subjects with anterior cruciate ligament deficiency (ACL-D), we examined proprioception, quadriceps strength, somatosensory evoked potentials (SEPs) and muscle responses during gait in varied combinations of speed and incline. Seventeen subjects with ACL-D were grouped by functional level and report of giving way. Seven subjects without ACL-D served as a control sample for muscle response measures. ACL-D subjects with quadriceps weakness experienced giving way and could not resume sport activities. Those without weakness fell into one of two groups: (1) copers, who had full return to previous activity and no giving way despite proprioceptive loss and altered SEPs, and (2) adapters, who were unable to return to previous activity level and experienced giving way despite neither proprioceptive loss or altered SEPs. The unique muscle pattern in copers during inclined fast walking included larger and earlier hamstring activation. These results suggest that in individuals with ACL-D without a strength deficit, altered SEPs and altered neuromuscular patterns are the factors that enable resumption of pre-injury functional levels. Loss of proprioception may drive the central changes, which in turn drives the development of altered muscle patterns.

  13. Dexmedetomidine ameliorates muscle wasting and attenuates the alteration of hypothalamic neuropeptides and inflammation in endotoxemic rats

    PubMed Central

    Cheng, Minhua; Gao, Tao; Xi, Fengchan; Cao, Chun; Chen, Yan; Zhao, Chenyan; Li, Qiurong

    2017-01-01

    Dexmedetomidine is generally used for sedaton in critically ill, it could shorten duration of mechanical ventilation, ICU stay and lower basic metabolism. However, the exact mechanism of these positive effects remains unkown. Here we investigated the hypothesis that dexmedetomidine could ameliorate muscle wasting in endotoxemic rats and whether it was related to hypothalamic neuropeptides alteration and inflammation. Fourty-eight adult male Sprague–Dawley rats were intraperitoneally injected with lipopolysaccharide (LPS) (5 mg/kg) or saline, followed by 50 μg/kg dexmedetomidine or saline administration via the femoral vein catheter (infusion at 5 μg·kg-1·hr-1). Twenty-four hours after injection, hypothalamus tissues and skeletal muscle were obtained. Muscle wasting was measured by the mRNA expression of two E3 ubiquitin ligases, muscle atrophy F-box (MAFbx) and muscle ring finger 1 (MuRF-1) as well as 3-methylhistidine (3-MH) and tyrosine release. Hypothalamic inflammatory markers and neuropeptides expression were also detected in all four groups. Results showed that LPS administration led to significant increase in hypothalamic inflammation together with muscle wasting. Increased hypothalamic neuropeptides, proopiomelanocortin (POMC), cocaine and amphetamine-related transcript (CART) and neuropeptides Y (NPY) and decreased agouti-related protein (AgRP) were also observed. Meanwhile dexmedetomidine administration ameliorated muscle wasting, hypothalamic inflammation and modulated the alteration of neuropeptides, POMC, CART and AgRP, in endotoxemic rats. In conclusion, dexmedetomidine could alleviate muscle wasting in endotoxemic rats, and it could also attenuate the alteration of hypothalamic neuropeptides and reduce hypothalamic inflammation. PMID:28358856

  14. Neuropathic Pain-like Alterations in Muscle Nociceptor Function Associated with Vibration-induced Muscle Pain

    PubMed Central

    Chen, Xiaojie; Green, Paul G.; Levine, Jon D.

    2010-01-01

    We recently developed a rodent model of the painful muscle disorders induced by occupational exposure to vibration. In the present study we used this model to evaluate the function of sensory neurons innervating the vibration-exposed gastrocnemius muscle. Activity of 74 vibration-exposed and 40 control nociceptors, with mechanical receptive fields in the gastrocnemius muscle, were recorded. In vibration-exposed rats ~15% of nociceptors demonstrated an intense and long-lasting barrage of action potentials in response to sustained suprathreshold mechanical stimulation (average of 2635 action potentials with frequency of ~44 Hz during a 1 minute suprathreshold stimulus) much greater than has been reported to be produced even by potent inflammatory mediators. While these high-firing nociceptors had lower mechanical thresholds than the remaining nociceptors, exposure to vibration had no effect on conduction velocity and did not induce spontaneous activity. Hyperactivity was not observed in any of 19 neurons from vibration exposed rats pretreated with intrathecal antisense for the IL-6 receptor subunit gp130. Since vibration can injure peripheral nerves, and IL-6 has been implicated in painful peripheral neuropathies, we suggest that the dramatic change in sensory neuron function and development of muscles pain, induced by exposure to vibration, reflects a neuropathic muscle pain syndrome. PMID:20800357

  15. Menopause alters temperature sensitivity of muscle force in humans.

    PubMed

    Bieles, J S; Bruce, S A; Woledge, R C

    2012-03-01

    Isometric maximum voluntary force (MVF) of the adductor pollicis and first dorsal interosseous muscles was measured in 11 pre- and 11 post-menopausal (Pre-M and Post-M) human subjects. The temperature of the hand varied in the range 18°-38°C by water immersion and skin temperature was recorded. MVF at each temperature was expressed relative to the value at skin temperature above 35°C to give MVF(REL). The form of the relation between MVF(REL) and temperature was different in the Pre-M and Post-M groups (p < 0.01). In the Pre-M group the maximum value of MVF(REL) occurred near 30°C and force fell at both higher and lower temperatures. In the Post-M group MVF(REL) showed an approximately linear decline with cooling across the whole temperature range. The maximum value of MVF(REL) for the Post-M group was near 35°C. The values of MVF(REL) for the Post-M group were significantly lower than for the Pre-M group at temperatures between 18° and 30°C.

  16. Morphological Alterations in Gastrocnemius and Soleus Muscles in Male and Female Mice in a Fibromyalgia Model.

    PubMed

    Bonaterra, Gabriel Alejandro; Then, Hanna; Oezel, Lisa; Schwarzbach, Hans; Ocker, Matthias; Thieme, Kati; Di Fazio, Pietro; Kinscherf, Ralf

    2016-01-01

    Fibromyalgia (FM) is a chronic musculoskeletal pain disorder, characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances, however often with unknown etiology. According to recent reports, physical and psychological stress trigger FM. To develop new treatments for FM, experimental animal models for FM are needed to be development and characterized. Using a mouse model for FM including intermittent cold stress (ICS), we hypothesized that ICS leads to morphological alterations in skeletal muscles in mice. Male and female ICS mice were kept under alternating temperature (4 °C/room temperature [22 °C]); mice constantly kept at room temperature served as control. After scarification, gastrocnemius and soleus muscles were removed and snap-frozen in liquid nitrogen-cooled isopentane or fixed for electron microscopy. In gastrocnemius/soleus muscles of male ICS mice, we found a 21.6% and 33.2% decrease of fiber cross sectional area (FCSA), which in soleus muscle concerns the loss of type IIa and IIx FCSA. This phenomenon was not seen in muscles of female ICS mice. However, this loss in male ICS mice was associated with an increase in gastrocnemius of the density of MIF+ (8.6%)-, MuRF+ (14.7%)-, Fbxo32+ (17.8%)-cells, a 12.1% loss of capillary contacts/muscle fiber as well as a 30.7% increase of damaged mitochondria in comparison with male control mice. Moreover, significant positive correlations exist among densities (n/mm(2)) of MIF+, MuRF+, Fbxo32+-cells in gastrocnemius/ soleus muscles of male ICS mice; these cell densities inversely correlate with FCSA especially in gastrocnemius muscle of male ICS mice. The ICS-induced decrease of FCSA mainly concerns gastrocnemius muscle of male mice due to an increase of inflammatory and atrogenic cells. In soleus muscle of male ICS and soleus/gastrocnemius muscles of female ICS mice morphological alterations seem to occur not at all or delayed. The sex-specificity of findings

  17. Morphological Alterations in Gastrocnemius and Soleus Muscles in Male and Female Mice in a Fibromyalgia Model

    PubMed Central

    Oezel, Lisa; Schwarzbach, Hans; Ocker, Matthias; Thieme, Kati; Di Fazio, Pietro; Kinscherf, Ralf

    2016-01-01

    Background Fibromyalgia (FM) is a chronic musculoskeletal pain disorder, characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances, however often with unknown etiology. According to recent reports, physical and psychological stress trigger FM. To develop new treatments for FM, experimental animal models for FM are needed to be development and characterized. Using a mouse model for FM including intermittent cold stress (ICS), we hypothesized that ICS leads to morphological alterations in skeletal muscles in mice. Methods Male and female ICS mice were kept under alternating temperature (4°C/room temperature [22°C]); mice constantly kept at room temperature served as control. After scarification, gastrocnemius and soleus muscles were removed and snap-frozen in liquid nitrogen–cooled isopentane or fixed for electron microscopy. Results In gastrocnemius/soleus muscles of male ICS mice, we found a 21.6% and 33.2% decrease of fiber cross sectional area (FCSA), which in soleus muscle concerns the loss of type IIa and IIx FCSA. This phenomenon was not seen in muscles of female ICS mice. However, this loss in male ICS mice was associated with an increase in gastrocnemius of the density of MIF+ (8.6%)-, MuRF+ (14.7%)-, Fbxo32+ (17.8%)-cells, a 12.1% loss of capillary contacts/muscle fiber as well as a 30.7% increase of damaged mitochondria in comparison with male control mice. Moreover, significant positive correlations exist among densities (n/mm2) of MIF+, MuRF+, Fbxo32+-cells in gastrocnemius/ soleus muscles of male ICS mice; these cell densities inversely correlate with FCSA especially in gastrocnemius muscle of male ICS mice. Conclusion The ICS-induced decrease of FCSA mainly concerns gastrocnemius muscle of male mice due to an increase of inflammatory and atrogenic cells. In soleus muscle of male ICS and soleus/gastrocnemius muscles of female ICS mice morphological alterations seem to occur not at all or

  18. Misexpression of a Chloroplast Aspartyl Protease Leads to Severe Growth Defects and Alters Carbohydrate Metabolism in Arabidopsis1[C][W

    PubMed Central

    Paparelli, Eleonora; Gonzali, Silvia; Parlanti, Sandro; Novi, Giacomo; Giorgi, Federico M.; Licausi, Francesco; Kosmacz, Monika; Feil, Regina; Lunn, John E.; Brust, Henrike; van Dongen, Joost T.; Steup, Martin; Perata, Pierdomenico

    2012-01-01

    The crucial role of carbohydrate in plant growth and morphogenesis is widely recognized. In this study, we describe the characterization of nana, a dwarf Arabidopsis (Arabidopsis thaliana) mutant impaired in carbohydrate metabolism. We show that the nana dwarf phenotype was accompanied by altered leaf morphology and a delayed flowering time. Our genetic and molecular data indicate that the mutation in nana is due to a transfer DNA insertion in the promoter region of a gene encoding a chloroplast-located aspartyl protease that alters its pattern of expression. Overexpression of the gene (oxNANA) phenocopies the mutation. Both nana and oxNANA display alterations in carbohydrate content, and the extent of these changes varies depending on growth light intensity. In particular, in low light, soluble sugar levels are lower and do not show the daily fluctuations observed in wild-type plants. Moreover, nana and oxNANA are defective in the expression of some genes implicated in sugar metabolism and photosynthetic light harvesting. Interestingly, some chloroplast-encoded genes as well as genes whose products seem to be involved in retrograde signaling appear to be down-regulated. These findings suggest that the NANA aspartic protease has an important regulatory function in chloroplasts that not only influences photosynthetic carbon metabolism but also plastid and nuclear gene expression. PMID:22987884

  19. Altered motor unit discharge patterns in paretic muscles of stroke survivors assessed using surface electromyography

    NASA Astrophysics Data System (ADS)

    Hu, Xiaogang; Suresh, Aneesha K.; Rymer, William Z.; Suresh, Nina L.

    2016-08-01

    Objective. Hemispheric stroke survivors often show impairments in voluntary muscle activation. One potential source of these impairments could come from altered control of muscle, via disrupted motor unit (MU) firing patterns. In this study, we sought to determine whether MU firing patterns are modified on the affected side of stroke survivors, as compared with the analogous contralateral muscle. Approach. Using a novel surface electromyogram (EMG) sensor array, coupled with advanced template recognition software (dEMG) we recorded surface EMG signals over the first dorsal interosseous (FDI) muscle on both paretic and contralateral sides. Recordings were made as stroke survivors produced isometric index finger abductions over a large force range (20%-60% of maximum). Utilizing the dEMG algorithm, MU firing rates, recruitment thresholds, and action potential amplitudes were estimated for concurrently active MUs in each trial. Main results. Our results reveal significant changes in the firing rate patterns in paretic FDI muscle, in that the discharge rates, characterized in relation to recruitment force threshold and to MU size, were less clearly correlated with recruitment force than in contralateral FDI muscles. Firing rates in the affected muscle also did not modulate systematically with the level of voluntary muscle contraction, as would be expected in intact muscles. These disturbances in firing properties also correlated closely with the impairment of muscle force generation. Significance. Our results provide strong evidence of disruptions in MU firing behavior in paretic muscles after a hemispheric stroke, suggesting that modified control of the spinal motoneuron pool could be a contributing factor to muscular weakness in stroke survivors.

  20. Collagen content does not alter the passive mechanical properties of fibrotic skeletal muscle in mdx mice.

    PubMed

    Smith, Lucas R; Barton, Elisabeth R

    2014-05-15

    Many skeletal muscle diseases are associated with progressive fibrosis leading to impaired muscle function. Collagen within the extracellular matrix is the primary structural protein providing a mechanical scaffold for cells within tissues. During fibrosis collagen not only increases in amount but also undergoes posttranslational changes that alter its organization that is thought to contribute to tissue stiffness. Little, however, is known about collagen organization in fibrotic muscle and its consequences for function. To investigate the relationship between collagen content and organization with muscle mechanical properties, we studied mdx mice, a model for Duchenne muscular dystrophy (DMD) that undergoes skeletal muscle fibrosis, and age-matched control mice. We determined collagen content both histologically, with picosirius red staining, and biochemically, with hydroxyproline quantification. Collagen content increased in the mdx soleus and diaphragm muscles, which was exacerbated by age in the diaphragm. Collagen packing density, a parameter of collagen organization, was determined using circularly polarized light microscopy of picosirius red-stained sections. Extensor digitorum longus (EDL) and soleus muscle had proportionally less dense collagen in mdx muscle, while the diaphragm did not change packing density. The mdx muscles had compromised strength as expected, yet only the EDL had a significantly increased elastic stiffness. The EDL and diaphragm had increased dynamic stiffness and a change in relative viscosity. Unexpectedly, passive stiffness did not correlate with collagen content and only weakly correlated with collagen organization. We conclude that muscle fibrosis does not lead to increased passive stiffness and that collagen content is not predictive of muscle stiffness. Copyright © 2014 the American Physiological Society.

  1. Studies on the possible role of thyroid hormone in altered muscle protein turnover during sepsis

    SciTech Connect

    Hasselgren, P.O.; Chen, I.W.; James, J.H.; Sperling, M.; Warner, B.W.; Fischer, J.E.

    1987-07-01

    Five days after thyroidectomy (Tx) or sham-Tx in young male Sprague-Dawley rats, sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent laparotomy and manipulation of the cecum without ligation or puncture. Sixteen hours after CLP or laparotomy, protein synthesis and degradation were measured in incubated extensor digitorum longus (EDL) and soleus (SOL) muscles by determining rate of /sup 14/C-phenylalanine incorporation into protein and tyrosine release into incubation medium, respectively. Triiodothyronine (T3) was measured in serum and muscle tissue. Protein synthesis was reduced by 39% and 22% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx rats. The response to sepsis of protein synthesis was abolished in Tx rats. Protein breakdown was increased by 113% and 68% in EDL and SOL, respectively, 16 hours after CLP in sham-Tx animals. The increase in muscle proteolysis during sepsis was blunted in hypothyroid animals and was 42% and 49% in EDL and SOL, respectively. T3 in serum was reduced by sepsis, both in Tx and sham-Tx rats. T3 in muscle, however, was maintained or increased during sepsis. Abolished or blunted response of muscle protein turnover after CLP in hypothyroid animals may reflect a role of thyroid hormones in altered muscle protein metabolism during sepsis. Reduced serum levels of T3, but maintained or increased muscle concentrations of the hormone, suggests that increased T3 uptake by muscle may be one mechanism of low T3 syndrome in sepsis, further supporting the concept of a role for thyroid hormone in metabolic alterations in muscle during sepsis.

  2. Altered Skeletal Muscle Mitochondrial Proteome As the Basis of Disruption of Mitochondrial Function in Diabetic Mice

    PubMed Central

    Zabielski, Piotr; Lanza, Ian R.; Gopala, Srinivas; Holtz Heppelmann, Carrie J.; Bergen, H. Robert; Dasari, Surendra

    2016-01-01

    Insulin plays pivotal role in cellular fuel metabolism in skeletal muscle. Despite being the primary site of energy metabolism, the underlying mechanism on how insulin deficiency deranges skeletal muscle mitochondrial physiology remains to be fully understood. Here we report an important link between altered skeletal muscle proteome homeostasis and mitochondrial physiology during insulin deficiency. Deprivation of insulin in streptozotocin-induced diabetic mice decreased mitochondrial ATP production, reduced coupling and phosphorylation efficiency, and increased oxidant emission in skeletal muscle. Proteomic survey revealed that the mitochondrial derangements during insulin deficiency were related to increased mitochondrial protein degradation and decreased protein synthesis, resulting in reduced abundance of proteins involved in mitochondrial respiration and β-oxidation. However, a paradoxical upregulation of proteins involved in cellular uptake of fatty acids triggered an accumulation of incomplete fatty acid oxidation products in skeletal muscle. These data implicate a mismatch of β-oxidation and fatty acid uptake as a mechanism leading to increased oxidative stress in diabetes. This notion was supported by elevated oxidative stress in cultured myotubes exposed to palmitate in the presence of a β-oxidation inhibitor. Together, these results indicate that insulin deficiency alters the balance of proteins involved in fatty acid transport and oxidation in skeletal muscle, leading to impaired mitochondrial function and increased oxidative stress. PMID:26718503

  3. Alterations in Skeletal Muscle Microcirculation of Head-Down Tilted Rats

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Stepke, Bernhard; Fleming, John T.; Joshua, Irving G.

    1992-01-01

    In this study we assessed the function of microscopic blood vessels in skeletal muscle (cremaster muscle) for alterations which may contribute to the observed elevation of blood pressure associated with head-down tilted whole body suspension (HDT/WBS), a model of weightlessness. Arteriolar baseline diameters, vasoconstrictor responses to norepinephrine (NE) and vasodilation to nitroprusside (NP) were assessed in control rats, rats suspended for 7 or 14 day HDT/WBS rats, and rats allowed to recover for 1 day after 7 days HDT/WBS. Neither baseline diameters nor ability to dilate were influenced by HDT/WBS. Maximum vasoconstriction to norepinephrine was significantly greater in arterioles of hypertensive 14 day HDT/WBS rats. This first study of the intact microvasculature in skeletal muscle indicates that an elevated contractility of arterioles to norepinephrine in suspended rats, and suggests an elevated peripheral resistance in striated muscle may contribute to the increase in blood pressures among animals subjected to HDT/WBS.

  4. Effects of altered loading states on muscle plasticity: what have we learned from rodents?

    NASA Technical Reports Server (NTRS)

    Baldwin, K. M.

    1996-01-01

    This paper summarizes the key findings concerning the adaptive properties of rodent muscle in response to altered loading states. When the mechanical stress on the muscle is chronically increased, the muscle adapts by hypertrophying its fibers. This response is regulated by processes resulting in contractile protein expression reflecting slower phenotypes, thereby enabling the muscle to better support load-hearing activity. In contrast, reducing the load-bearing activity induces an opposite response whereby muscles used for both antigravity function and locomotion atrophy while transforming some of the slow fibers into faster contractile phenotypes. Accompanying the atrophy is both a reduced power generating and activity sustaining capability. These adaptive processes are regulated by both transcriptional and translational processes. Available evidence further suggests that the interaction of heavy resistance activity and hormonal/growth factors (insulin-like growth factor, growth hormone, glucocorticoids, etc.) are critical in the maintenance of muscle mass and function. Also resistance training, in contrast to other activities such as endurance running, provides a more economical form of stress because less mechanical activity is required to maintain muscle homeostasis in the context of chronic states of weightlessness.

  5. Effects of altered loading states on muscle plasticity: what have we learned from rodents?

    NASA Technical Reports Server (NTRS)

    Baldwin, K. M.

    1996-01-01

    This paper summarizes the key findings concerning the adaptive properties of rodent muscle in response to altered loading states. When the mechanical stress on the muscle is chronically increased, the muscle adapts by hypertrophying its fibers. This response is regulated by processes resulting in contractile protein expression reflecting slower phenotypes, thereby enabling the muscle to better support load-hearing activity. In contrast, reducing the load-bearing activity induces an opposite response whereby muscles used for both antigravity function and locomotion atrophy while transforming some of the slow fibers into faster contractile phenotypes. Accompanying the atrophy is both a reduced power generating and activity sustaining capability. These adaptive processes are regulated by both transcriptional and translational processes. Available evidence further suggests that the interaction of heavy resistance activity and hormonal/growth factors (insulin-like growth factor, growth hormone, glucocorticoids, etc.) are critical in the maintenance of muscle mass and function. Also resistance training, in contrast to other activities such as endurance running, provides a more economical form of stress because less mechanical activity is required to maintain muscle homeostasis in the context of chronic states of weightlessness.

  6. Effects of altered loading states on muscle plasticity: what have we learned from rodents?

    PubMed

    Baldwin, K M

    1996-10-01

    This paper summarizes the key findings concerning the adaptive properties of rodent muscle in response to altered loading states. When the mechanical stress on the muscle is chronically increased, the muscle adapts by hypertrophying its fibers. This response is regulated by processes resulting in contractile protein expression reflecting slower phenotypes, thereby enabling the muscle to better support load-hearing activity. In contrast, reducing the load-bearing activity induces an opposite response whereby muscles used for both antigravity function and locomotion atrophy while transforming some of the slow fibers into faster contractile phenotypes. Accompanying the atrophy is both a reduced power generating and activity sustaining capability. These adaptive processes are regulated by both transcriptional and translational processes. Available evidence further suggests that the interaction of heavy resistance activity and hormonal/growth factors (insulin-like growth factor, growth hormone, glucocorticoids, etc.) are critical in the maintenance of muscle mass and function. Also resistance training, in contrast to other activities such as endurance running, provides a more economical form of stress because less mechanical activity is required to maintain muscle homeostasis in the context of chronic states of weightlessness.

  7. Protein restriction during gestation alters histone modifications at the glucose transporter 4 (GLUT4) promoter region and induces GLUT4 expression in skeletal muscle of female rat offspring.

    PubMed

    Zheng, Shasha; Rollet, Michelle; Pan, Yuan-Xiang

    2012-09-01

    Maternal nutrition during pregnancy is an intrauterine factor that results in alteration of the offspring genome and associates with disease risk in the offspring. We investigated the impact of a maternal low-protein (LP) diet on the expression of glucose transporter 4 (GLUT4) in offspring skeletal muscle. GLUT4 is an insulin-regulated glucose transporter involved in insulin sensitivity and carbohydrate metabolism in muscle cells. We observed sex-dependent GLUT4 mRNA expression and increased GLUT4 protein content in female pup skeletal muscle with maternal LP. Analysis of transcriptional and epigenetic regulation of increased skeletal muscle GLUT4 expression in offspring rats revealed the regulatory mechanisms involved. The protein level of myocyte enhancer factor 2A (MEF2A), which has been known as an activator of GLUT4 transcription via the ability to carry out specific binding to the GLUT4 MEF2 binding sequence, increased in female pups whose mothers were fed a LP diet. Modifications of chromatin structure, including acetylated histone H3, acetylated histone H4 and di-methylated histone H3 at lysine 4, were detected at a significantly increased level at the GLUT4 promoter region in female pup muscle following a maternal LP diet. Glycogen content was also detected as up-regulated, accompanied by increased glycogen synthase in LP female offspring muscle. These results document that maternal protein restriction during pregnancy induces GLUT4 expression in female offspring skeletal muscle but not in males, which may indicate sex-dependent adaptation of glucose metabolism to a maternal LP diet.

  8. Structural and functional alterations of muscle fibres in the novel mouse model of facioscapulohumeral muscular dystrophy.

    PubMed

    D'Antona, Giuseppe; Brocca, Lorenza; Pansarasa, Orietta; Rinaldi, Chiara; Tupler, Rossella; Bottinelli, Roberto

    2007-11-01

    We recently generated a mouse model of facioscapulohumeral muscular dystrophy (FSHD) by selectively overexpressing FRG1, a candidate gene for FSHD, in skeletal muscle. The muscles of the FRG-1 mice did not show any plasmamembrane defect suggesting a novel pathogenetic mechanism for FSHD. Here, we study structure and function of muscle fibres from three lines of mice overexpressing FRG1 at different levels: FRG1-low, FRG1-med, FRG1-high. Cross-sectional area (CSA), specific force (Po/CSA) and maximum shortening velocity (V(o)) of identified types of muscle fibres from FRG1-low and FRG1-med mice were analysed and found to be lower than in WT mice. Fast fibres and especially type 2B fibres (the fastest type) were preferentially involved in the dystrophic process showing a much larger force deficit than type 1 (slow) fibres. Consistent with the latter observation, the MHC isoform distribution of several muscles of the three FRG1 lines showed a shift towards slower MHC isoforms in comparison to WT muscle. Moreover, fast muscles showed a more evident histological deterioration, a larger atrophy and a higher percentage of centrally nucleated fibres than the soleus, the slowest muscle in mice. Interestingly, loss in CSA, Po/CSA and V(o) of single muscle fibres and MHC isoform shift towards a slower phenotype can be considered early signs of muscular dystrophy (MD). They were, in fact, found also in FRG1-low mice which did not show any impairment of function in vivo and of muscle size in vitro and in soleus muscles, which had a completely preserved morphology. This study provides a detailed characterization of structure and function of muscle fibres in a novel murine model of one of the main human MDs and suggests that fundamental features of the dystrophic process, common to most MDs, such as the intrinsic loss of contractile strength of muscle fibres, the preferential involvement of fast fibres and the shift towards a slow muscle phenotype can occur independently from

  9. Investigations of the Effects of Altered Vestibular System Function on Hindlimb Anti-Gravity Muscles

    NASA Technical Reports Server (NTRS)

    Lowery, Mary Sue

    1998-01-01

    Exposure to different gravitational environments, both the microgravity of spaceflight and the hypergravity of centrifugation, result in altered vestibulo-spinal function which can be reversed by reacclimation to earth gravity (2). Control of orientation, posture, and locomotion are functions of the vestibular system which are altered by changes in gravitational environment. Not only is the vestibular system involved with coordination and proprioception, but the gravity sensing portion of the vestibular system also plays a major role in maintaining muscle tone through projections to spinal cord motoneurons that control anti-gravity muscles. I have been involved with investigations of several aspects of the link between vestibular inputs and muscle morphology and function during my work with Dr. Nancy Daunton this summer and the previous summer. We have prepared a manuscript for submission (4) to Aviation, Space, and Environmental Medicine based on work that I performed last summer in Dr. Daunton's lab. Techniques developed for that project will be utilized in subsequent experiments begun in the summer of 1998. I have been involved with the development of a pilot project to test the effects of vestibular galvanic stimulation (VGS) on anti-gravity muscles and in another project testing the effects of the ototoxic drug streptomycin on the otolith-spinal reflex and anti-gravity muscle morphology.

  10. Investigations of the Effects of Altered Vestibular System Function on Hindlimb Anti-Gravity Muscles

    NASA Technical Reports Server (NTRS)

    Lowery, Mary Sue

    1998-01-01

    Exposure to different gravitational environments, both the microgravity of spaceflight and the hypergravity of centrifugation, result in altered vestibulo-spinal function which can be reversed by reacclimation to earth gravity (2). Control of orientation, posture, and locomotion are functions of the vestibular system which are altered by changes in gravitational environment. Not only is the vestibular system involved with coordination and proprioception, but the gravity sensing portion of the vestibular system also plays a major role in maintaining muscle tone through projections to spinal cord motoneurons that control anti-gravity muscles. I have been involved with investigations of several aspects of the link between vestibular inputs and muscle morphology and function during my work with Dr. Nancy Daunton this summer and the previous summer. We have prepared a manuscript for submission (4) to Aviation, Space, and Environmental Medicine based on work that I performed last summer in Dr. Daunton's lab. Techniques developed for that project will be utilized in subsequent experiments begun in the summer of 1998. I have been involved with the development of a pilot project to test the effects of vestibular galvanic stimulation (VGS) on anti-gravity muscles and in another project testing the effects of the ototoxic drug streptomycin on the otolith-spinal reflex and anti-gravity muscle morphology.

  11. Intensified exercise training does not alter AMPK signaling in human skeletal muscle.

    PubMed

    Clark, S A; Chen, Z-P; Murphy, K T; Aughey, R J; McKenna, M J; Kemp, B E; Hawley, J A

    2004-05-01

    The AMP-activated protein kinase (AMPK) cascade has been linked to many of the acute effects of exercise on skeletal muscle substrate metabolism, as well as to some of the chronic training-induced adaptations. We determined the effect of 3 wk of intensified training (HIT; 7 sessions of 8 x 5 min at 85% Vo2 peak) in skeletal muscle from well-trained athletes on AMPK responsiveness to exercise. Rates of whole body substrate oxidation were determined during a 90-min steady-state ride (SS) pre- and post-HIT. Muscle metabolites and AMPK signaling were determined from biopsies taken at rest and immediately after exercise during the first and seventh HIT sessions, performed at the same (absolute) pre-HIT work rate. HIT decreased rates of whole body carbohydrate oxidation (P < 0.05) and increased rates of fat oxidation (P < 0.05) during SS. Resting muscle glycogen and its utilization during intense exercise were unaffected by HIT. However, HIT induced a twofold decrease in muscle [lactate] (P < 0.05) and resulted in tighter metabolic regulation, i.e., attenuation of the decrease in the PCr/(PCr + Cr) ratio and of the increase in [AMPfree]/ATP. Resting activities of AMPKalpha1 and -alpha2 were similar post-HIT, with the magnitude of the rise in response to exercise similar pre- and post-HIT. AMPK phosphorylation at Thr172 on both the alpha1 and alpha2 subunits increased in response to exercise, with the magnitude of this rise being similar post-HIT. Acetyl-coenzyme A carboxylase-beta phosphorylation was similar at rest and, despite HIT-induced increases in whole body rates of fat oxidation, did not increase post-HIT. Our results indicate that, in well-trained individuals, short-term HIT improves metabolic control but does not blunt AMPK signaling in response to intense exercise.

  12. Alterations of the Deltoid Muscle After Open Versus Arthroscopic Rotator Cuff Repair.

    PubMed

    Cho, Nam Su; Cha, Sang Won; Rhee, Yong Girl

    2015-12-01

    Open repair can be more useful than arthroscopic repair for immobile and severely retracted, large to massive rotator cuff tears. However, it is not known whether the deltoid muscle is altered after open repair or to what extent the deltoid origin remains detached after surgery. To compare postoperative alterations of the deltoid muscle in open versus arthroscopic repair for severely retracted, large to massive rotator cuff tears. Case-control study; Level of evidence, 3. Enrolled in this study were 135 patients who underwent surgical repair for severely retracted, large to massive rotator cuff tears and who had routine follow-up MRIs at least 6 months after surgery. Open repairs were performed in 56 cases and arthroscopic repairs in 79 cases. The detachment and thickness of the deltoid muscle at its proximal origin were recorded in 5 zones on MRI. The alterations of the deltoid muscle and postoperative integrity of the repaired rotator cuff were evaluated. Partial detachment of the deltoid occurred in 1 patient (1.8%) in the open group and in 2 patients (2.5%) in the arthroscopic group (P = .80). All the partial detachments occurred in zones 2 and 3. Attenuation of the proximal origin of the deltoid was found in 3 patients (5.4%) in the open group and in 4 patients (5.1%) in the arthroscopic group (P = .87). Atrophy of the deltoid muscle was shown in 3 patients (5.4%) in the open group and 4 patients (5.1%) in the arthroscopic group (P = .61). The retear rate of the repaired cuff was 30.4% (17/56) in the open group and 38.0% (30/79) in the arthroscopic group (P = .74). Between open and arthroscopic repair for severely retracted, large to massive rotator cuff tears, there was no significant difference in detachment of the deltoid origin and alterations of the deltoid muscle after repair. Postoperative alterations of the deltoid occurred in arthroscopic surgery as well as in open surgery. For immobile massive rotator cuff tear, open repair is an acceptable technique

  13. Alterations in Skeletal Muscle Cell Homeostasis in a Mouse Model of Cigarette Smoke Exposure

    PubMed Central

    Caron, Marc-André; Morissette, Mathieu C.; Thériault, Marie-Eve; Nikota, Jake K.; Stämpfli, Martin R.; Debigaré, Richard

    2013-01-01

    Background Skeletal muscle dysfunction is common in chronic obstructive pulmonary disease (COPD), a disease mainly caused by chronic cigarette use. An important proportion of patients with COPD have decreased muscle mass, suggesting that chronic cigarette smoke exposure may interfere with skeletal muscle cellular equilibrium. Therefore, the main objective of this study was to investigate the kinetic of the effects that cigarette smoke exposure has on skeletal muscle cell signaling involved in protein homeostasis and to assess the reversibility of these effects. Methods A mouse model of cigarette smoke exposure was used to assess skeletal muscle changes. BALB/c mice were exposed to cigarette smoke or room air for 8 weeks, 24 weeks or 24 weeks followed by 60 days of cessation. The gastrocnemius and soleus muscles were collected and the activation state of key mediators involved in protein synthesis and degradation was assessed. Results Gastrocnemius and soleus were smaller in mice exposed to cigarette smoke for 8 and 24 weeks compared to room air exposed animals. Pro-degradation proteins were induced at the mRNA level after 8 and 24 weeks. Twenty-four weeks of cigarette smoke exposure induced pro-degradation proteins and reduced Akt phosphorylation and glycogen synthase kinase-3β quantity. A 60-day smoking cessation period reversed the cell signaling alterations induced by cigarette smoke exposure. Conclusions Repeated cigarette smoke exposure induces reversible muscle signaling alterations that are dependent on the duration of the cigarette smoke exposure. These results highlights a beneficial aspect associated with smoking cessation. PMID:23799102

  14. Absence of Aquaporin-4 in Skeletal Muscle Alters Proteins Involved in Bioenergetic Pathways and Calcium Handling

    PubMed Central

    Basco, Davide; Nicchia, Grazia Paola; D'Alessandro, Angelo; Zolla, Lello; Svelto, Maria; Frigeri, Antonio

    2011-01-01

    Aquaporin-4 (AQP4) is a water channel expressed at the sarcolemma of fast-twitch skeletal muscle fibers, whose expression is altered in several forms of muscular dystrophies. However, little is known concerning the physiological role of AQP4 in skeletal muscle and its functional and structural interaction with skeletal muscle proteome. Using AQP4-null mice, we analyzed the effect of the absence of AQP4 on the morphology and protein composition of sarcolemma as well as on the whole skeletal muscle proteome. Immunofluorescence analysis showed that the absence of AQP4 did not perturb the expression and cellular localization of the dystrophin-glycoprotein complex proteins, aside from those belonging to the extracellular matrix, and no alteration was found in sarcolemma integrity by dye extravasation assay. With the use of a 2DE-approach (BN/SDS-PAGE), protein maps revealed that in quadriceps, out of 300 Coomassie-blue detected and matched spots, 19 proteins exhibited changed expression in AQP4−/− compared to WT mice. In particular, comparison of the protein profiles revealed 12 up- and 7 down-regulated protein spots in AQP4−/− muscle. Protein identification by MS revealed that the perturbed expression pattern belongs to proteins involved in energy metabolism (i.e. GAPDH, creatine kinase), as well as in Ca2+ handling (i.e. parvalbumin, SERCA1). Western blot analysis, performed on some significantly changed proteins, validated the 2D results. Together these findings suggest AQP4 as a novel determinant in the regulation of skeletal muscle metabolism and better define the role of this water channel in skeletal muscle physiology. PMID:21552523

  15. Absence of aquaporin-4 in skeletal muscle alters proteins involved in bioenergetic pathways and calcium handling.

    PubMed

    Basco, Davide; Nicchia, Grazia Paola; D'Alessandro, Angelo; Zolla, Lello; Svelto, Maria; Frigeri, Antonio

    2011-04-28

    Aquaporin-4 (AQP4) is a water channel expressed at the sarcolemma of fast-twitch skeletal muscle fibers, whose expression is altered in several forms of muscular dystrophies. However, little is known concerning the physiological role of AQP4 in skeletal muscle and its functional and structural interaction with skeletal muscle proteome. Using AQP4-null mice, we analyzed the effect of the absence of AQP4 on the morphology and protein composition of sarcolemma as well as on the whole skeletal muscle proteome. Immunofluorescence analysis showed that the absence of AQP4 did not perturb the expression and cellular localization of the dystrophin-glycoprotein complex proteins, aside from those belonging to the extracellular matrix, and no alteration was found in sarcolemma integrity by dye extravasation assay. With the use of a 2DE-approach (BN/SDS-PAGE), protein maps revealed that in quadriceps, out of 300 Coomassie-blue detected and matched spots, 19 proteins exhibited changed expression in AQP4(-/-) compared to WT mice. In particular, comparison of the protein profiles revealed 12 up- and 7 down-regulated protein spots in AQP4-/- muscle. Protein identification by MS revealed that the perturbed expression pattern belongs to proteins involved in energy metabolism (i.e. GAPDH, creatine kinase), as well as in Ca(2+) handling (i.e. parvalbumin, SERCA1). Western blot analysis, performed on some significantly changed proteins, validated the 2D results. Together these findings suggest AQP4 as a novel determinant in the regulation of skeletal muscle metabolism and better define the role of this water channel in skeletal muscle physiology.

  16. Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity

    PubMed Central

    Shanely, R. Andrew; Nieman, David C.; Perkins-Veazie, Penelope; Henson, Dru A.; Meaney, Mary P.; Knab, Amy M.; Cialdell-Kam, Lynn

    2016-01-01

    Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM) contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years) participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125). Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05), however, the rating of perceived exertion was greater during the WM trial (p > 0.05). WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05), but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine), antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function. PMID:27556488

  17. Low-carbohydrate, high-protein, high-fat diet alters small peripheral artery reactivity in metabolic syndrome patients.

    PubMed

    Merino, Jordi; Kones, Richard; Ferré, Raimon; Plana, Núria; Girona, Josefa; Aragonés, Gemma; Ibarretxe, Daiana; Heras, Mercedes; Masana, Luis

    2014-01-01

    Low carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or metabolic syndrome (MS), their net effect on vascular function remains unclear. Evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery vascular function, in a cohort of MS patients. This cross-sectional study included 160 MS patients. Diet was evaluated by a 3-day food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1; 45% carbohydrate, 19% protein, 31% fat) had higher saRHI values than those in the top quartile (Q4; 30% carbohydrate, 25% protein, 43% fat) (1.84±0.42 vs. 1.55±0.25, P=.012). These results were similar in T2D patients (Q1=1.779±0.311 vs. Q4=1.618±0.352, P=.011) and also in all of the MS components, except for low HDLc. Multivariate analysis demonstrated that individuals in the highest LCDS quartile, that is, consuming less carbohydrates, had a significantly negative coefficient of saRHI which was independent of confounders (HR: -0.747; 95%CI: 0.201, 0.882; P=.029). These data suggest that a dietary pattern characterized by a low amount of carbohydrate, but reciprocally higher amounts of fat and protein, is associated with poorer vascular reactivity in patients with MS and T2D. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  18. Comparison of Watermelon and Carbohydrate Beverage on Exercise-Induced Alterations in Systemic Inflammation, Immune Dysfunction, and Plasma Antioxidant Capacity.

    PubMed

    Shanely, R Andrew; Nieman, David C; Perkins-Veazie, Penelope; Henson, Dru A; Meaney, Mary P; Knab, Amy M; Cialdell-Kam, Lynn

    2016-08-22

    Consuming carbohydrate- and antioxidant-rich fruits during exercise as a means of supporting and enhancing both performance and health is of interest to endurance athletes. Watermelon (WM) contains carbohydrate, lycopene, l-citrulline, and l-arginine. WM may support exercise performance, augment antioxidant capacity, and act as a countermeasure to exercise-induced inflammation and innate immune changes. Trained cyclists (n = 20, 48 ± 2 years) participated in a randomized, placebo controlled, crossover study. Subjects completed two 75 km cycling time trials after either 2 weeks ingestion of 980 mL/day WM puree or no treatment. Subjects drank either WM puree containing 0.2 gm/kg carbohydrate or a 6% carbohydrate beverage every 15 min during the time trials. Blood samples were taken pre-study and pre-, post-, 1 h post-exercise. WM ingestion versus no treatment for 2-weeks increased plasma l-citrulline and l-arginine concentrations (p < 0.0125). Exercise performance did not differ between WM puree or carbohydrate beverage trials (p > 0.05), however, the rating of perceived exertion was greater during the WM trial (p > 0.05). WM puree versus carbohydrate beverage resulted in a similar pattern of increase in blood glucose, and greater increases in post-exercise plasma antioxidant capacity, l-citrulline, l-arginine, and total nitrate (all p < 0.05), but without differences in systemic markers of inflammation or innate immune function. Daily WM puree consumption fully supported the energy demands of exercise, and increased post-exercise blood levels of WM nutritional components (l-citrulline and l-arginine), antioxidant capacity, and total nitrate, but without an influence on post-exercise inflammation and changes in innate immune function.

  19. Alterations in human muscle protein metabolism with aging: Protein and exercise as countermeasures to offset sarcopenia.

    PubMed

    Churchward-Venne, Tyler A; Breen, Leigh; Phillips, Stuart M

    2014-01-01

    Aging is associated with a reduction in skeletal muscle mass-sarcopenia-the etiology of which is multifactorial. One mechanism is that aging has, as one of its hallmarks, a reduced sensitivity of skeletal muscle to the normally potent anabolic effects of protein feeding and resistance exercise, and to the anticatabolic effects of insulin, the combination of which has been termed "anabolic resistance." However, this reduced sensitivity of skeletal muscle to anabolic stimuli may, in some cases, be overcome by providing a greater quantity of the nutrition and/or exercise stimulus. Daily habitual physical activity appears to be a primary determinant of anabolic resistance as we have recently shown that as little as 14 days of reduced ambulatory activity was sufficient to induce anabolic resistance in the elderly by attenuating the postprandial increase in muscle protein synthesis (MPS). The etiology of anabolic resistance is complex and may include alterations in amino acid uptake/utilization, cell signaling status, muscle blood flow, and microvascular perfusion (impacting amino acid delivery and availability). Further, there appears to be sexual dimorphism with advancing age in the response of MPS to amino acid/insulin provision. Maintenance of physical activity during aging is of fundamental importance for skeletal muscle to allow it to appropriately respond to the anabolic effects of nutrition.

  20. Hypercortisolemia alters muscle protein anabolism following ingestion of essential amino acids

    NASA Technical Reports Server (NTRS)

    Paddon-Jones, Douglas; Sheffield-Moore, Melinda; Creson, Daniel L.; Sanford, Arthur P.; Wolf, Steven E.; Wolfe, Robert R.; Ferrando, Arny A.

    2003-01-01

    Debilitating injury is accompanied by hypercortisolemia, muscle wasting, and disruption of the normal anabolic response to food. We sought to determine whether acute hypercortisolemia alters muscle protein metabolism following ingestion of a potent anabolic stimulus: essential amino acids (EAA). A 27-h infusion (80 microg. kg(-1). h(-1)) of hydrocortisone sodium succinate mimicked cortisol (C) levels accompanying severe injury (>30 microg/dl), (C + AA; n = 6). The control group (AA) received intravenous saline (n = 6). Femoral arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 micromol/kg) constant infusion (0.05 micromol. kg(-1). min(-1)) of l-[ring-(2)H(5)]phenylalanine before and after ingestion of 15 g of EAA. Hypercortisolemia [36.5 +/- 2.1 (C + AA) vs. 9.0 +/- 1.0 microg/dl (AA)] increased postabsorptive arterial, venous, and muscle intracellular phenylalanine concentrations. Hypercortisolemia also increased postabsorptive and post-EAA insulin concentrations. Net protein balance was blunted (40% lower) following EAA ingestion but remained positive for a greater period of time (60 vs. 180 min) in the C + AA group. Thus, although differences in protein metabolism were evident, EAA ingestion improved muscle protein anabolism during acute hypercortisolemia and may help minimize muscle loss following debilitating injury.

  1. Hypercortisolemia alters muscle protein anabolism following ingestion of essential amino acids

    NASA Technical Reports Server (NTRS)

    Paddon-Jones, Douglas; Sheffield-Moore, Melinda; Creson, Daniel L.; Sanford, Arthur P.; Wolf, Steven E.; Wolfe, Robert R.; Ferrando, Arny A.

    2003-01-01

    Debilitating injury is accompanied by hypercortisolemia, muscle wasting, and disruption of the normal anabolic response to food. We sought to determine whether acute hypercortisolemia alters muscle protein metabolism following ingestion of a potent anabolic stimulus: essential amino acids (EAA). A 27-h infusion (80 microg. kg(-1). h(-1)) of hydrocortisone sodium succinate mimicked cortisol (C) levels accompanying severe injury (>30 microg/dl), (C + AA; n = 6). The control group (AA) received intravenous saline (n = 6). Femoral arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 micromol/kg) constant infusion (0.05 micromol. kg(-1). min(-1)) of l-[ring-(2)H(5)]phenylalanine before and after ingestion of 15 g of EAA. Hypercortisolemia [36.5 +/- 2.1 (C + AA) vs. 9.0 +/- 1.0 microg/dl (AA)] increased postabsorptive arterial, venous, and muscle intracellular phenylalanine concentrations. Hypercortisolemia also increased postabsorptive and post-EAA insulin concentrations. Net protein balance was blunted (40% lower) following EAA ingestion but remained positive for a greater period of time (60 vs. 180 min) in the C + AA group. Thus, although differences in protein metabolism were evident, EAA ingestion improved muscle protein anabolism during acute hypercortisolemia and may help minimize muscle loss following debilitating injury.

  2. A 3-day high-fat/low-carbohydrate diet does not alter exercise-induced growth hormone response in healthy males.

    PubMed

    Sasaki, Hiroto; Ishibashi, Aya; Tsuchiya, Yoshihumi; Shimura, Nobuhiro; Kurihara, Toshiyuki; Ebi, Kumiko; Goto, Kazushige

    2015-12-01

    The purpose of the present study was to examine the effects of 3 days isoenergetic high-fat/low-carbohydrate diet (HF-LC) relative to low-fat/high-carbohydrate diet (LF-HC) on the exercise-induced growth hormone (GH) response in healthy male subjects. Ten healthy young males participated in this study. Each subject consumed the HF-LC (18±1% protein, 61±2% fat, 21±1% carbohydrate, 2720 kcal per day) for 3 consecutive days after consuming the LF-HC (18±1% protein, 20±1% fat, 62±1% carbohydrate, 2755 kcal per day) for 3 consecutive days. After each dietary intervention period, the hormonal and metabolic responses to an acute exercise (30 min of continuous pedaling at 60% of V˙O2max) were compared. The intramyocellular lipid (IMCL) contents in the vastus lateralis, soleus, and tibialis anterior were evaluated by proton magnetic resonance spectroscopy. Serum GH concentrations increased significantly during the exercise after both the HF-LC and LF-HC periods (P<0.05). However, the exercise-induced GH response was not significantly different between the two periods. Fat utilization and lipolytic responses during the exercise were enhanced significantly after the HF-LC period compared with the LF-HC period. IMCL content did not differ significantly in any portion of muscle after the dietary interventions. We could not show that short-term HF-LC consumption changed significantly exercise-induced GH response or IMCL content in healthy young males. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Altering source or amount of dietary carbohydrate has acute and chronic effects on postprandial glucose and triglycerides in type 2 diabetes: Canadian trial of Carbohydrates in Diabetes (CCD).

    PubMed

    Wolever, T M S; Gibbs, A L; Chiasson, J-L; Connelly, P W; Josse, R G; Leiter, L A; Maheux, P; Rabasa-Lhoret, R; Rodger, N W; Ryan, E A

    2013-03-01

    Nutrition recommendations for type 2 diabetes (T2DM) are partly guided by the postprandial responses elicited by diets varying in carbohydrate (CHO). We aimed to explore whether long-term changes in postprandial responses on low-glycemic-index (GI) or low-CHO diets were due to acute or chronic effects in T2DM. Subjects with diet-alone-treated T2DM were randomly assigned to high-CHO/high-GI (H), high-CHO/low-GI (L), or low-CHO/high-monounsaturated-fat (M) diets for 12-months. At week-0 (Baseline) postprandial responses after H-meals (55% CHO, GI = 61) were measured from 0800 h to 1600 h. After 12 mo subjects were randomly assigned to H-meals or study diet meals (L, 57% CHO, GI = 50; M, 44% CHO, GI = 61). This yielded 5 groups: H diet with H-meals (HH, n = 34); L diet with H- (LH, n = 17) or L-meals (LL, n = 16); and M diet with H- (MH, n = 18) or M meals (MM, n = 19). Postprandial glucose fluctuations were lower in LL than all other groups (p < 0.001). Changes in postprandial-triglycerides differed among groups (p < 0.001). After 12 mo in HH and MM both fasting- and postprandial-triglycerides were similar to Baseline while in MH postprandial-triglycerides were significantly higher than at Baseline (p = 0.028). In LH, triglycerides were consistently (0.18-0.34 mmol/L) higher than Baseline throughout the day, while in LL the difference from Baseline varied across the day from 0.04 to 0.36 mmol/L (p < 0.001). Low-GI and low-CHO diets have both acute and chronic effects on postprandial glucose and triglycerides in T2DM subjects. Thus, the composition of the acute test-meal and the habitual diet should be considered when interpreting the nutritional implications of different postprandial responses. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Effects of an ad libitum, high carbohydrate diet and aerobic exercise training on insulin action and muscle metabolism in older men and women.

    PubMed

    Hays, Nicholas P; Starling, Raymond D; Sullivan, Dennis H; Fluckey, James D; Coker, Robert H; Williams, Rick H; Evans, William J

    2006-03-01

    Previous studies have demonstrated that aerobic exercise training and weight loss have independent effects on insulin-stimulated glucose disposal (ISGD). We hypothesized that ad libitum consumption of a high-carbohydrate diet would result in weight loss and improved ISGD, and that aerobic exercise training would facilitate greater improvements in ISGD compared with diet alone. Older participants (13 women, 9 men; age = 66 +/- 1 year) with impaired glucose tolerance were randomly assigned to an ad libitum diet alone (18% fat, 19% protein, 63% carbohydrate) or this diet plus aerobic exercise training (4 d/wk, 45 min/d, 80% VO(2peak)) for 12 weeks. ISGD, abdominal fat distribution, muscle glycogen, and glycogen synthase activity were assessed pre- and postintervention. Consumption of the diet resulted in significant weight loss and an improvement in ISGD. Consumption of the diet plus exercise training also resulted in weight loss and increased ISGD, but results were not significantly different from those in the diet-alone group. Mean abdominal visceral and subcutaneous adipose tissue cross-sectional areas were smaller postintervention compared to baseline with no difference between groups. Exercise training and consumption of the diet increased muscle glycogen content (344.7 +/- 21.3 to 616.7 +/- 34.4 micromol.g(-1)) and decreased glycogen synthase activity (0.21 +/- 0.02 to 0.13 +/- 0.01) compared to the diet alone. These results demonstrate that consumption of an ad libitum, high-carbohydrate diet alone or in combination with aerobic exercise training results in weight loss and improved insulin sensitivity. Furthermore, exercise combined with this diet appears to limit additional increases in insulin sensitivity due to muscle glycogen supercompensation with a concomitant adaptive response of glycogen synthase.

  5. Prophylactic knee bracing alters lower-limb muscle forces during a double-leg drop landing.

    PubMed

    Ewing, Katie A; Fernandez, Justin W; Begg, Rezaul K; Galea, Mary P; Lee, Peter V S

    2016-10-03

    Anterior cruciate ligament (ACL) injury can be a painful, debilitating and costly consequence of participating in sporting activities. Prophylactic knee bracing aims to reduce the number and severity of ACL injury, which commonly occurs during landing maneuvers and is more prevalent in female athletes, but a consensus on the effectiveness of prophylactic knee braces has not been established. The lower-limb muscles are believed to play an important role in stabilizing the knee joint. The purpose of this study was to investigate the changes in lower-limb muscle function with prophylactic knee bracing in male and female athletes during landing. Fifteen recreational athletes performed double-leg drop landing tasks from 0.30m and 0.60m with and without a prophylactic knee brace. Motion analysis data were used to create subject-specific musculoskeletal models in OpenSim. Static optimization was performed to calculate the lower-limb muscle forces. A linear mixed model determined that the hamstrings and vasti muscles produced significantly greater flexion and extension torques, respectively, and greater peak muscle forces with bracing. No differences in the timings of peak muscle forces were observed. These findings suggest that prophylactic knee bracing may help to provide stability to the knee joint by increasing the active stiffness of the hamstrings and vasti muscles later in the landing phase rather than by altering the timing of muscle forces. Further studies are necessary to quantify whether prophylactic knee bracing can reduce the load placed on the ACL during intense dynamic movements. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Lingual Muscle Activity Across Sleep–Wake States in Rats with Surgically Altered Upper Airway

    PubMed Central

    Rukhadze, Irma; Kalter, Julie; Stettner, Georg M.; Kubin, Leszek

    2014-01-01

    Obstructive sleep apnea (OSA) patients have increased upper airway muscle activity, including such lingual muscles as the genioglossus (GG), geniohyoid (GH), and hyoglossus (HG). This adaptation partially protects their upper airway against obstructions. Rodents are used to study the central neural control of sleep and breathing but they do not naturally exhibit OSA. We investigated whether, in chronically instrumented, behaving rats, disconnecting the GH and HG muscles from the hyoid (H) apparatus would result in a compensatory increase of other upper airway muscle activity (electromyogram, EMG) and/or other signs of upper airway instability. We first determined that, in intact rats, lingual (GG and intrinsic) muscles maintained stable activity levels when quantified based on 2 h-long recordings conducted on days 6 through 22 after instrumentation. We then studied five rats in which the tendons connecting the GH and HG muscles to the H apparatus were experimentally severed. When quantified across all recording days, lingual EMG during slow-wave sleep (SWS) was modestly but significantly increased in rats with surgically altered upper airway [8.6 ± 0.7% (SE) vs. 6.1 ± 0.7% of the mean during wakefulness; p = 0.012]. Respiratory modulation of lingual EMG occurred mainly during SWS and was similarly infrequent in both groups, and the incidence of sighs and central apneas also was similar. Thus, a weakened action of selected lingual muscles did not produce sleep-disordered breathing but resulted in a relatively elevated activity in other lingual muscles during SWS. These results encourage more extensive surgical manipulations with the aim to obtain a rodent model with collapsible upper airway. PMID:24803913

  7. Characterizing the glycocalyx of poultry spermatozoa; semen cryopreservation methods alter the carbohydrate component of rooster sperm membrane glycoconjugates

    USDA-ARS?s Scientific Manuscript database

    The carbohydrate-rich zone on the sperm surface is essential for inmunoprotection in the female tract and early gamete interactions. We recently have shown the glycocalyx of chicken sperm to be extensively sialylated and contain residues of mannose, glucose, galactose, fucose, N-acetyl-galactosamine...

  8. Host-Adaptation of Francisella tularensis Alters the Bacterium's Surface-Carbohydrates to Hinder Effectors of Innate and Adaptive Immunity

    PubMed Central

    Zarrella, Tiffany M.; Singh, Anju; Bitsaktsis, Constantine; Rahman, Tabassum; Sahay, Bikash; Feustel, Paul J.; Gosselin, Edmund J.; Sellati, Timothy J.; Hazlett, Karsten R. O.

    2011-01-01

    Background The gram-negative bacterium Francisella tularensis survives in arthropods, fresh water amoeba, and mammals with both intracellular and extracellular phases and could reasonably be expected to express distinct phenotypes in these environments. The presence of a capsule on this bacterium has been controversial with some groups finding such a structure while other groups report that no capsule could be identified. Previously we reported in vitro culture conditions for this bacterium which, in contrast to typical methods, yielded a bacterial phenotype that mimics that of the bacterium's mammalian, extracellular phase. Methods/Findings SDS-PAGE and carbohydrate analysis of differentially-cultivated F. tularensis LVS revealed that bacteria displaying the host-adapted phenotype produce both longer polymers of LPS O-antigen (OAg) and additional HMW carbohydrates/glycoproteins that are reduced/absent in non-host-adapted bacteria. Analysis of wildtype and OAg-mutant bacteria indicated that the induced changes in surface carbohydrates involved both OAg and non-OAg species. To assess the impact of these HMW carbohydrates on the access of outer membrane constituents to antibody we used differentially-cultivated bacteria in vitro to immunoprecipitate antibodies directed against outer membrane moieties. We observed that the surface-carbohydrates induced during host–adaptation shield many outer membrane antigens from binding by antibody. Similar assays with normal mouse serum indicate that the induced HMW carbohydrates also impede complement deposition. Using an in vitro macrophage infection assay, we find that the bacterial HMW carbohydrate impedes TLR2-dependent, pro-inflammatory cytokine production by macrophages. Lastly we show that upon host-adaptation, the human-virulent strain, F. tularensis SchuS4 also induces capsule production with the effect of reducing macrophage-activation and accelerating tularemia pathogenesis in mice. Conclusion F. tularensis undergoes

  9. A Potential Gravity-Sensing Role of Vascular Smooth Muscle Cell Glycocalyx in Altered Gravitational Stimulation

    PubMed Central

    Kang, Hongyan; Liu, Meili

    2013-01-01

    Abstract Previously, we have shown that vascular smooth muscle cells (VSMCs) exhibit varied physiological responses when exposed to altered gravitational conditions. In the present study, we focused on elucidating whether the cell surface glycocalyx could be a potential gravity sensor. For this purpose, a roller culture apparatus was used with the intent to provide altered gravitational conditions to cultured rat aortic smooth muscle cells (RASMCs). Heparinase III (Hep.III) was applied to degrade cell surface heparan sulfate proteoglycans (HSPG) selectively. Sodium chlorate was used to suppress new synthesis of HSPG. Glycocalyx remodeling, nitric oxide synthase (NOS) activation, and F-actin expression induced by gravity alteration were assessed by flow cytometry, reverse transcription polymerase chain reaction (RT-PCR), and Western blot. Results indicate that the exposure of cultured RASMCs to altered gravitational conditions led to a reduction in cell surface HSPG content and the activation of NOS. It also down-regulated the expression of glypican-1, constitutive NOS (NOSI and NOSIII), and F-actin. On the other hand, Hep.III followed by sodium chlorate treatment of HSPG attenuated the aforementioned NOS and F-actin modulation under altered gravitational conditions. All these findings suggest that the glycocalyx, and HSPG in particular, may be an important sensor of gravitational changes. This may play an important role in the regulation of NOS activation, F-actin modulation, and HSPG remodeling in VSMCs. Key Words: Glycocalyx—Gravity sensor—Gravity alteration—Roller culture apparatus. Astrobiology 13, 626–636. PMID:23848471

  10. Heart failure alters matrix metalloproteinase gene expression and activity in rat skeletal muscle.

    PubMed

    Carvalho, Robson Francisco; Dariolli, Rafael; Justulin Junior, Luis Antonio; Sugizaki, Mário Mateus; Politi Okoshi, Marina; Cicogna, Antonio Carlos; Felisbino, Sérgio Luis; Dal Pai-Silva, Maeli

    2006-12-01

    Heart failure is associated with a skeletal muscle myopathy with cellular and extracellular alterations. The hypothesis of this investigation is that extracellular changes may be associated with enhanced mRNA expression and activity of matrix metalloproteinases (MMP). We examined MMP mRNA expression and MMP activity in Soleus (SOL), extensor digitorum longus (EDL), and diaphragm (DIA) muscles of young Wistar rat with monocrotaline-induced heart failure. Rats injected with saline served as age-matched controls. MMP2 and MMP9 mRNA contents were determined by RT-PCR and MMP activity by electrophoresis in gelatin-containing polyacrylamide gels in the presence of SDS under non-reducing conditions. Heart failure increased MMP9 mRNA expression and activity in SOL, EDL and DIA and MMP2 mRNA expression in DIA. These results suggest that MMP changes may contribute to the skeletal muscle myopathy during heart failure.

  11. Effects of altered muscle temperature on neuromuscular properties in young and older women.

    PubMed

    Dewhurst, Susan; Macaluso, Andrea; Gizzi, Leonardo; Felici, Francesco; Farina, Dario; De Vito, Giuseppe

    2010-02-01

    Muscle temperature has a profound effect on the neuromuscular system of young individuals, however, little is known about the effects of altered temperature on the muscles of older individuals. The purpose of this study was to investigate the effect of altered local temperature on maximal torque and electromyography signal characteristics in 15 young (21.5 +/- 2.2 years; mean +/- SD) and 12 older (73.6 +/- 3.2 years) women. Subjects completed maximal voluntary isometric knee extension and flexion, together with isokinetic knee extensions (30, 60, 90, 120 and 240 degrees/s) at three muscle temperatures: control (approximately 34 degrees C), cold (approximately 30 degrees C) and warm (approximately 38 degrees C). The torque was lower in the older compared to young subjects at all temperatures (range of difference for 240 degrees /s, 25-40%; P < 0.001). Warming had no effect on torque in either group, whereas cooling decreased the torque during the isokinetic contractions in the young group only (range of decrease 6-10%; P < 0.05). In both groups, muscle fibre conduction velocity was slower with cooling compared to the warm condition (-15% in the young and -17% in the older subjects; P < 0.05).Temperature, however, had no effect on the agonist-antagonist coactivation level or the rate of force development in either group. The results suggest that, in particular, cooling the muscles has a greater effect on motor performance in young than older adults, which may indicate reduced adaptation of the neuromuscular system of older adults to altered temperature.

  12. Alteration of inflammatory cytokines, energy metabolic regulators, and muscle fiber type in the skeletal muscle of postweaning piglets.

    PubMed

    Li, F; Li, Y; Tan, B; Wang, J; Duan, Y; Guo, Q; Liu, Y; Kong, X; Li, T; Tang, Y; Yin, Y

    2016-03-01

    This study was conducted to determine the alterations of inflammatory cytokines, energy metabolic regulators, and muscle fiber type in the LM of the piglets postweaning. Crossbred piglets (Landrace × Large White) weaned at 14 d age were randomly selected from 8 litters and slaughtered at 0 (W0), 1 (W1), 3 (W3), 5 (W5), or 7 (W7) days postweaning. The glycogen content, free glucose concentration, and enzyme activities, including ATPase (Na/K, Ca/Mg), creatine kinase, and lactic dehydrogenase (LDH), were detected in the skeletal muscle tissue. Concentrations of proinflammatory cytokines, including IL-1β, IL-6, and tumor necrosis factor-α (TNF-α), and anti-inflammatory cytokines, including IL-10 and transforming growth factor-β1 (TGF-β1), were measured in serum. The mRNA abundance of the above cytokines, energy metabolic regulators, and muscle fiber type related genes were determined via real-time quantitative PCR analysis. The adenosine monophosphate-activated protein kinase α (AMPKα) signaling was measured by Western blot analysis. Our results showed ATPase activities were lower on W7 d but LDH activity was higher on W3 d after weaning ( < 0.05). Serum TNF-α concentration was markedly increased on W1 d, then returned to the value of preweaning ( < 0.05), and almost all the values of inflammatory cytokines were reduced to a low point on W5 d after weaning. Additionally, the IL-6 mRNA abundance was upregulated during W3 to W7 d, but cytokine TNF-α was upregulated just on W7 d ( < 0.05). The mRNA abundance of AMPKα and uncoupling protein (UCP) 3 were both higher on W1 and W3 d, and UCP2 was higher on W7 d postweaning ( < 0.05). Myosin heavy chain (MyHC) I and MyHC IIx-type fibers were enhanced on W1 d, then returned to the value of preweaning, and the MyHC IIb-type fiber was significantly increased on W5 and W7 d ( < 0.05). Meanwhile, the value of P-AMPKα/T-AMPKα increased on W3 d postweaning ( < 0.05) compared with that on W0 d. These results indicate

  13. Muscle spindle alterations precede onset of sensorimotor deficits in Charcot-Marie-Tooth type 2E.

    PubMed

    Villalón, E; Jones, M R; Sibigtroth, C; Zino, S J; Dale, J M; Landayan, D S; Shen, H; Cornelison, D D W; Garcia, M L

    2017-02-01

    Charcot-Marie-Tooth (CMT) is the most common inherited peripheral neuropathy, affecting approximately 2.8 million people. The CMT leads to distal neuropathy that is characterized by reduced motor nerve conduction velocity, ataxia, muscle atrophy and sensory loss. We generated a mouse model of CMT type 2E (CMT2E) expressing human neurofilament light E396K (hNF-L(E396K) ), which develops decreased motor nerve conduction velocity, ataxia and muscle atrophy by 4 months of age. Symptomatic hNF-L(E396K) mice developed phenotypes that were consistent with proprioceptive sensory defects as well as reduced sensitivity to mechanical stimulation, while thermal sensitivity and auditory brainstem responses were unaltered. Progression from presymptomatic to symptomatic included a 50% loss of large diameter sensory axons within the fifth lumbar dorsal root of hNF-L(E396K) mice. Owing to proprioceptive deficits and loss of large diameter sensory axons, we analyzed muscle spindle morphology in presymptomatic and symptomatic hNF-L(E396K) and hNF-L control mice. Muscle spindle cross-sectional area and volume were reduced in all hNF-L(E396K) mice analyzed, suggesting that alterations in muscle spindle morphology occurred prior to the onset of typical CMT pathology. These data suggested that CMT2E pathology initiated in the muscle spindles altering the proprioceptive sensory system. Early sensory pathology in CMT2E could provide a unifying hypothesis for the convergence of pathology observed in CMT.

  14. Myopathic Alterations in Extraocular Muscle of Rats Subchronically Fed Pyridostigmine Bromide

    DTIC Science & Technology

    1990-01-01

    myasthenia gravis and could be used by U.S. mil- sis. Ultrastructurally, in muscles such as diaphragm, itary personnel and their allies as part of a...cleft were common features. This last feature has changes at the NMJ of diaphragm and soleus mus- been reported in human myasthenia gravis in the cles...greater sensitivity to PB, VA (1976). The motor end plate in myasthenia gravis as severe morphologic alterations are still present and in experimental

  15. Adults with initial metabolic syndrome have altered muscle deoxygenation during incremental exercise.

    PubMed

    Machado, Alessandro da Costa; Barbosa, Thales Coelho; Kluser Sales, Allan Robson; de Souza, Marcio Nogueira; da Nóbrega, Antonio Claudio Lucas; Silva, Bruno Moreira

    2017-02-01

    Reduced aerobic power is independently associated with metabolic syndrome (MetS) incidence and prevalence in adults. This study investigated whether muscle deoxygenation (proxy of microvascular O2 extraction) during incremental exercise is altered in MetS and associated with reduced oxygen consumption ( V˙O2peak ). Twelve men with initial MetS (no overt diseases and medication-naive; mean ± SD, age 38 ± 7 years) and 12 healthy controls (HCs) (34 ± 7 years) completed an incremental cycling test to exhaustion, in which pulmonary ventilation and gas exchange (metabolic analyzer), as well as vastus lateralis deoxygenation (near infrared spectroscopy), were measured. Subjects with MetS, in contrast to HCs, showed lower V˙O2peak normalized to total lean mass, similar V˙O2 response to exercise, and earlier break point (BP) in muscle deoxygenation. Consequently, deoxygenation slope from BP to peak exercise was greater. Furthermore, absolute V˙O2peak was positively associated with BP in correlations adjusted for total lean mass. MetS, without overt diseases, altered kinetics of muscle deoxygenation during incremental exercise, particularly at high-intensity exercise. Therefore, the balance between utilization and delivery of O2 within skeletal muscle is impaired early in MetS natural history, which may contribute to the reduction in aerobic power. © 2017 The Obesity Society.

  16. Changes in gluteal muscle forces with alteration of footstrike pattern during running.

    PubMed

    Vannatta, Charles Nathan; Kernozek, Thomas W; Gheidi, Naghmeh

    2017-08-09

    Gait retraining is a common form of treatment for running related injuries. Proximal factors at the hip have been postulated as having a role in the development of running related injuries. How altering footstrike affects hip muscles forces and kinematics has not been described. Thus, we aimed to quantify differences in hip muscle forces and hip kinematics that may occur when healthy runners are instructed to alter their foot strike pattern from their habitual rear-foot strike to a forefoot strike. This may gain insight on the potential etiology and treatment methods of running related lower extremity injury. Twenty-five healthy female runners completed a minimum of 10 running trials in a controlled laboratory setting under rear-foot strike and instructed forefoot strike conditions. Kinetic and kinematic data were used in an inverse dynamic based static optimization to estimate individual muscle forces during running. Within subject differences were investigated using a repeated measures multi-variate analysis of variance. Peak gluteus medius and minimus and hamstring forces were reduced while peak gluteus maximus force was increased when running with an instructed forefoot strike pattern. Peak hip adduction, hip internal rotation, and heel-COM distance were also reduced. Therefore, instructing habitual rearfoot strike runners to run with a forefoot strike pattern resulted in changes in peak gluteal and hamstring muscle forces and hip kinematics. These changes may be beneficial to the development and treatment of running related lower extremity injury. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Altered Myokine Secretion Is an Intrinsic Property of Skeletal Muscle in Type 2 Diabetes

    PubMed Central

    Ciaraldi, Theodore P.; Ryan, Alexander J.; Mudaliar, Sunder R.; Henry, Robert R.

    2016-01-01

    Skeletal muscle secretes factors, termed myokines. We employed differentiated human skeletal muscle cells (hSMC) cultured from Type 2 diabetic (T2D) and non-diabetic (ND) subjects to investigate the impact of T2D on myokine secretion. Following 24 hours of culture concentrations of selected myokines were determined to range over 4 orders of magnitude. T2D hSMC released increased amounts of IL6, IL8, IL15, TNFa, Growth Related Oncogene (GRO)a, monocyte chemotactic protein (MCP)-1, and follistatin compared to ND myotubes. T2D and ND hSMC secreted similar levels of IL1ß and vascular endothelial growth factor (VEGF). Treatment with the inflammatory agents lipopolysaccharide (LPS) or palmitate augmented the secretion of many myokines including: GROa, IL6, IL8, IL15, and TNFa, but did not consistently alter the protein content and/or phosphorylation of IkBa, p44/42 MAPK, p38 MAPK, c-Jun N-terminal kinase (JNK) and NF-kB, nor lead to consistent changes in basal and insulin-stimulated glucose uptake or free fatty acid oxidation. Conversely, treatment with pioglitazone or oleate resulted in modest reductions in the secretion of several myokines. Our results demonstrate that altered secretion of a number of myokines is an intrinsic property of skeletal muscle in T2D, suggesting a putative role of myokines in the response of skeletal muscle to T2D. PMID:27453994

  18. Alterations in skeletal muscle related to impaired physical mobility: an empirical model

    NASA Technical Reports Server (NTRS)

    Kasper, C. E.; McNulty, A. L.; Otto, A. J.; Thomas, D. P.

    1993-01-01

    The objective of this investigation was to study impaired physical mobility and the resulting skeletal muscle atrophy. An animal model was used to study morphological adaptations of the soleus and plantaris muscles to decreased loading induced by hindlimb suspension of an adult rat for 7, 14, and 28 consecutive days. Alterations in weight, skeletal muscle growth, and changes in fiber type composition were studied in synergistic plantar flexors of the rat hindlimb. Body weight and the soleus muscle mass to body mass ratio demonstrated significant progressive atrophy over th 28-day experimental period with the most significant changes occurring in the first 7 days of hindlimb suspension. Hindlimb suspension produced atrophy of Type I and Type IIa muscle fibers as demonstrated by significant decreases in fiber cross-sectional area (micron 2). These latter changes account for the loss of contractile force production reported in the rat following hindlimb unloading. When compared to traditional models of hindlimb suspension and immobilization, the ISC model produces a less severe atrophy while maintaining animal mobility and health. We conclude that it is the preferred animal model to address nursing questions of impaired physical mobility.

  19. Alteration of gene expression profiles in skeletal muscle of rats exposed to microgravity during a spaceflight

    NASA Technical Reports Server (NTRS)

    Taylor, Wayne E.; Bhasin, Shalender; Lalani, Rukhsana; Datta, Anuj; Gonzalez-Cadavid, Nestor F.

    2002-01-01

    To clarify the mechanism of skeletal muscle wasting during spaceflights, we investigated whether intramuscular gene expression profiles are affected, by using DNA microarray methods. Male rats sent on the 17-day NASA STS-90 Neurolab spaceflight were sacrificed 24 hours after return to earth (MG group). Ground control rats were maintained for 17 days in flight-simulated cages (CS group). Spaceflight induced a 19% and 23% loss of tibialis anterior and gastrocnemius muscle mass, respectively, as compared to ground controls. Muscle RNA was analyzed by the Clontech Atlas DNA expression array in four rats, with two MG/ CS pairs for the tibialis anterior, and one pair for the gastrocnemius. Alterations in gene expression were verified for selected genes by reverse-transcription PCR. In both muscles of MG rats, mRNAs for 12 genes were up-regulated by over 2-fold, and 38 were down-regulated compared to controls. There was inhibition of genes for cell proliferation and growth factor cascades, including cell cycle genes and signal transduction proteins, such as p21 Cip1, retinoblastoma (Rb), cyclins G1/S, -E and -D3, MAP kinase 3, MAD3, and ras related protein RAB2. These data indicate that following exposure to microgravity, there is downregulation of genes involved in regulation of muscle satellite cell replication.

  20. Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice

    PubMed Central

    Leduc-Gaudet, Jean-Philippe; Picard, Martin; Pelletier, Félix St-Jean; Sgarioto, Nicolas; Auger, Marie-Joëlle; Vallée, Joanne; Robitaille, Richard; St-Pierre, David H.; Gouspillou, Gilles

    2015-01-01

    Skeletal muscle aging is associated with a progressive decline in muscle mass and strength, a process termed sarcopenia. Evidence suggests that accumulation of mitochondrial dysfunction plays a causal role in sarcopenia, which could be triggered by impaired mitophagy. Mitochondrial function, mitophagy and mitochondrial morphology are interconnected aspects of mitochondrial biology, and may coordinately be altered with aging. However, mitochondrial morphology has remained challenging to characterize in muscle, and whether sarcopenia is associated with abnormal mitochondrial morphology remains unknown. Therefore, we assessed the morphology of SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria in skeletal muscle of young (8-12wk-old) and old (88-96wk-old) mice using a quantitative 2-dimensional transmission electron microscopy approach. We show that sarcopenia is associated with larger and less circular SS mitochondria. Likewise, aged IMF mitochondria were longer and more branched, suggesting increased fusion and/or decreased fission. Accordingly, although no difference in the content of proteins regulating mitochondrial dynamics (Mfn1, Mfn2, Opa1 and Drp1) was observed, a mitochondrial fusion index (Mfn2-to-Drp1 ratio) was significantly increased in aged muscles. Our results reveal that sarcopenia is associated with complex changes in mitochondrial morphology that could interfere with mitochondrial function and mitophagy, and thus contribute to aging-related accumulation of mitochondrial dysfunction and sarcopenia. PMID:26053100

  1. Alteration of gene expression profiles in skeletal muscle of rats exposed to microgravity during a spaceflight

    NASA Technical Reports Server (NTRS)

    Taylor, Wayne E.; Bhasin, Shalender; Lalani, Rukhsana; Datta, Anuj; Gonzalez-Cadavid, Nestor F.

    2002-01-01

    To clarify the mechanism of skeletal muscle wasting during spaceflights, we investigated whether intramuscular gene expression profiles are affected, by using DNA microarray methods. Male rats sent on the 17-day NASA STS-90 Neurolab spaceflight were sacrificed 24 hours after return to earth (MG group). Ground control rats were maintained for 17 days in flight-simulated cages (CS group). Spaceflight induced a 19% and 23% loss of tibialis anterior and gastrocnemius muscle mass, respectively, as compared to ground controls. Muscle RNA was analyzed by the Clontech Atlas DNA expression array in four rats, with two MG/ CS pairs for the tibialis anterior, and one pair for the gastrocnemius. Alterations in gene expression were verified for selected genes by reverse-transcription PCR. In both muscles of MG rats, mRNAs for 12 genes were up-regulated by over 2-fold, and 38 were down-regulated compared to controls. There was inhibition of genes for cell proliferation and growth factor cascades, including cell cycle genes and signal transduction proteins, such as p21 Cip1, retinoblastoma (Rb), cyclins G1/S, -E and -D3, MAP kinase 3, MAD3, and ras related protein RAB2. These data indicate that following exposure to microgravity, there is downregulation of genes involved in regulation of muscle satellite cell replication.

  2. Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice.

    PubMed

    Leduc-Gaudet, Jean-Philippe; Picard, Martin; St-Jean Pelletier, Félix; Sgarioto, Nicolas; Auger, Marie-Joëlle; Vallée, Joanne; Robitaille, Richard; St-Pierre, David H; Gouspillou, Gilles

    2015-07-20

    Skeletal muscle aging is associated with a progressive decline in muscle mass and strength, a process termed sarcopenia. Evidence suggests that accumulation of mitochondrial dysfunction plays a causal role in sarcopenia, which could be triggered by impaired mitophagy. Mitochondrial function, mitophagy and mitochondrial morphology are interconnected aspects of mitochondrial biology, and may coordinately be altered with aging. However, mitochondrial morphology has remained challenging to characterize in muscle, and whether sarcopenia is associated with abnormal mitochondrial morphology remains unknown. Therefore, we assessed the morphology of SubSarcolemmal (SS) and InterMyoFibrillar (IMF) mitochondria in skeletal muscle of young (8-12wk-old) and old (88-96wk-old) mice using a quantitative 2-dimensional transmission electron microscopy approach. We show that sarcopenia is associated with larger and less circular SS mitochondria. Likewise, aged IMF mitochondria were longer and more branched, suggesting increased fusion and/or decreased fission. Accordingly, although no difference in the content of proteins regulating mitochondrial dynamics (Mfn1, Mfn2, Opa1 and Drp1) was observed, a mitochondrial fusion index (Mfn2-to-Drp1 ratio) was significantly increased in aged muscles. Our results reveal that sarcopenia is associated with complex changes in mitochondrial morphology that could interfere with mitochondrial function and mitophagy, and thus contribute to aging-related accumulation of mitochondrial dysfunction and sarcopenia.

  3. Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance

    PubMed Central

    Brandon, Amanda E.; Tid-Ang, Jennifer; Wright, Lauren E.; Stuart, Ella; Suryana, Eurwin; Bentley, Nicholas; Turner, Nigel; Cooney, Gregory J.; Ruderman, Neil B.; Kraegen, Edward W.

    2015-01-01

    SIRT1 is a NAD+-dependent deacetylase thought to regulate cellular metabolic pathways in response to alterations in nutrient flux. In the current study we investigated whether acute changes in SIRT1 expression affect markers of muscle mitochondrial content and also determined whether SIRT1 influenced muscle insulin resistance induced by acute glucose oversupply. In male Wistar rats either SIRT1 or a deacetylase inactive mutant form (H363Y) was electroprated into the tibialis cranialis (TC) muscle. The other leg was electroporated with an empty control vector. One week later, glucose was infused and hyperglycaemia was maintained at ~11mM. After 5 hours, 11mM glucose induced significant insulin resistance in skeletal muscle. Interestingly, overexpression of either SIRT1 or SIRT1 (H363Y) for 1 week did not change markers of mitochondrial content or function. SIRT1 or SIRT1 (H363Y) overexpression had no effect on the reduction in glucose uptake and glycogen synthesis in muscle in response to hyperglycemia. Therefore we conclude that acute increases in SIRT1 protein have little impact on mitochondrial content and that overexpressing SIRT1 does not prevent the development of insulin resistance during hyperglycaemia. PMID:25798922

  4. Ultrastructural alterations in skeletal muscle of pigs with acute monensin myotoxicosis.

    PubMed Central

    Van Vleet, J. F.; Ferrans, V. J.

    1984-01-01

    Large doses of monensin, a Na+-selective carboxylic ionophore, produce polyfocal, monophasic necrosis of skeletal muscle, with Type I fiber selectivity, in swine. For a study of the sequential ultrastructural alterations in affected skeletal muscles, 14 weanling pigs were given 40 mg monensin/kg body weight and were euthanatized 1, 2, 4, 8, and 16 days later. Myotoxicosis and myoglobinuria were apparent clinically. At necropsy, white, dry areas of necrosis were present in the muscle masses of the anterior and posterior thigh, shoulder, and loin. Two patterns of skeletal muscle necrosis were observed on Day 1, especially in Type I fibers. In fibers exhibiting the first of these patterns, the contractile material was disrupted, forming dense amorphous and filamentous clumps scattered within the persistent sheaths of external lamina (sarcolemmal tubes); the mitochondria were swollen and contained flocculent matrix densities, and the nuclei were pyknotic. Fibers showing the second pattern were uniformly dense, but their sarcoplasm was not disrupted. Sublethally injured fibers were also observed and showed focal myofibrillar lysis. On Days 2 and 4, the necrotic muscle had marked infiltration of macrophages in the interstitium and within sarcolemmal tubes. Rapid resolution of the fiber necrosis occurred by phagocytosis of the sarcoplasmic debris. Regeneration of affected muscles developed early following injury and progressed rapidly to complete restoration of the necrotic muscles without residual fibrosis. Regeneration was initiated on Day 1 by activation of satellite cells to form presumptive myoblasts; on Days 4 and 8 these cells showed evidence of fusion, forming myotubes to restore the necrotic fibers. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:6696050

  5. Locomotor Muscle Fatigue Does Not Alter Oxygen Uptake Kinetics during High-Intensity Exercise

    PubMed Central

    Hopker, James G.; Caporaso, Giuseppe; Azzalin, Andrea; Carpenter, Roger; Marcora, Samuele M.

    2016-01-01

    The V˙O2 slow component (V˙O2sc) that develops during high-intensity aerobic exercise is thought to be strongly associated with locomotor muscle fatigue. We sought to experimentally test this hypothesis by pre-fatiguing the locomotor muscles used during subsequent high-intensity cycling exercise. Over two separate visits, eight healthy male participants were asked to either perform a non-metabolically stressful 100 intermittent drop-jumps protocol (pre-fatigue condition) or rest for 33 min (control condition) according to a random and counterbalanced order. Locomotor muscle fatigue was quantified with 6-s maximal sprints at a fixed pedaling cadence of 90 rev·min−1. Oxygen kinetics and other responses (heart rate, capillary blood lactate concentration and rating of perceived exertion, RPE) were measured during two subsequent bouts of 6 min cycling exercise at 50% of the delta between the lactate threshold and V˙O2max determined during a preliminary incremental exercise test. All tests were performed on the same cycle ergometer. Despite significant locomotor muscle fatigue (P = 0.03), the V˙O2sc was not significantly different between the pre-fatigue (464 ± 301 mL·min−1) and the control (556 ± 223 mL·min−1) condition (P = 0.50). Blood lactate response was not significantly different between conditions (P = 0.48) but RPE was significantly higher following the pre-fatiguing exercise protocol compared with the control condition (P < 0.01) suggesting higher muscle recruitment. These results demonstrate experimentally that locomotor muscle fatigue does not significantly alter the V˙O2 kinetic response to high intensity aerobic exercise, and challenge the hypothesis that the V˙O2sc is strongly associated with locomotor muscle fatigue. PMID:27790156

  6. Altering the Structure of Carbohydrate Storage Granules in the Cyanobacterium Synechocystis sp. Strain PCC 6803 through Branching-Enzyme Truncations

    PubMed Central

    Welkie, David G.; Lee, Byung-Hoo

    2015-01-01

    ABSTRACT Carbohydrate storage is an important element of metabolism in cyanobacteria and in the chloroplasts of plants. Understanding how to manipulate the metabolism and storage of carbohydrate is also an important factor toward harnessing cyanobacteria for energy production. While most cyanobacteria produce glycogen, some have been found to accumulate polysaccharides in the form of water-insoluble α-glucan similar to amylopectin. Notably, this alternative form, termed “semi-amylopectin,” forms in cyanobacterial species harboring three branching-enzyme (BE) homologs, designated BE1, BE2, and BE3. In this study, mutagenesis of the branching genes found in Synechocystis sp. strain PCC 6803 was performed in order to characterize their possible impact on polysaccharide storage granule morphology. N-terminal truncations were made to the native BE gene of Synechocystis sp. PCC 6803. In addition, one of the two native debranching enzyme genes was replaced with a heterologous debranching enzyme gene from a semi-amylopectin-forming strain. Growth and glycogen content of mutant strains did not significantly differ from those of the wild type, and ultrastructure analysis revealed only slight changes to granule morphology. However, analysis of chain length distribution by anion-exchange chromatography revealed modest changes to the branched-chain length profile. The resulting glycogen shared structure characteristics similar to that of granules isolated from semi-amylopectin-producing strains. IMPORTANCE This study is the first to investigate the impact of branching-enzyme truncations on the structure of storage carbohydrates in cyanobacteria. The results of this study are an important contribution toward understanding the relationship between the enzymatic repertoire of a cyanobacterial species and the morphology of its storage carbohydrates. PMID:26668264

  7. Altering the Structure of Carbohydrate Storage Granules in the Cyanobacterium Synechocystis sp. Strain PCC 6803 through Branching-Enzyme Truncations.

    PubMed

    Welkie, David G; Lee, Byung-Hoo; Sherman, Louis A

    2015-12-14

    Carbohydrate storage is an important element of metabolism in cyanobacteria and in the chloroplasts of plants. Understanding how to manipulate the metabolism and storage of carbohydrate is also an important factor toward harnessing cyanobacteria for energy production. While most cyanobacteria produce glycogen, some have been found to accumulate polysaccharides in the form of water-insoluble α-glucan similar to amylopectin. Notably, this alternative form, termed "semi-amylopectin," forms in cyanobacterial species harboring three branching-enzyme (BE) homologs, designated BE1, BE2, and BE3. In this study, mutagenesis of the branching genes found in Synechocystis sp. strain PCC 6803 was performed in order to characterize their possible impact on polysaccharide storage granule morphology. N-terminal truncations were made to the native BE gene of Synechocystis sp. PCC 6803. In addition, one of the two native debranching enzyme genes was replaced with a heterologous debranching enzyme gene from a semi-amylopectin-forming strain. Growth and glycogen content of mutant strains did not significantly differ from those of the wild type, and ultrastructure analysis revealed only slight changes to granule morphology. However, analysis of chain length distribution by anion-exchange chromatography revealed modest changes to the branched-chain length profile. The resulting glycogen shared structure characteristics similar to that of granules isolated from semi-amylopectin-producing strains. This study is the first to investigate the impact of branching-enzyme truncations on the structure of storage carbohydrates in cyanobacteria. The results of this study are an important contribution toward understanding the relationship between the enzymatic repertoire of a cyanobacterial species and the morphology of its storage carbohydrates. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Understanding Carbohydrates

    MedlinePlus

    ... Size: A A A Listen En Español Understanding Carbohydrates How much and what type of carbohydrate foods ... glucose levels in your target range. Explore: Understanding Carbohydrates Glycemic Index and Diabetes Learn about the glycemic ...

  9. Lactate dehydrogenase expression at the onset of altered loading in rat soleus muscle.

    PubMed

    Washington, Tyrone A; Reecy, James M; Thompson, Raymond W; Lowe, Larry L; McClung, Joseph M; Carson, James A

    2004-10-01

    Both functional overload and hindlimb disuse induce significant energy-dependent remodeling of skeletal muscle. Lactate dehydrogenase (LDH), an important enzyme involved in anaerobic glycolysis, catalyzes the interconversion of lactate and pyruvate critical for meeting rapid high-energy demands. The purpose of this study was to determine rat soleus LDH-A and -B isoform expression, mRNA abundance, and enzymatic activity at the onset of increased or decreased loading in the rat soleus muscle. The soleus muscles from male Sprague-Dawley rats were functionally overloaded for up to 3 days by a modified synergist ablation or subjected to disuse by hindlimb suspension for 3 days. LDH mRNA concentration was determined by Northern blotting, LDH protein isoenzyme composition was determined by zymogram analysis, and LDH enzymatic activity was determined spectrophotometrically. LDH-A mRNA abundance increased by 372%, and LDH-B mRNA abundance decreased by 43 and 31% after 24 h and 3 days of functional overload, respectively, compared with that in control rats. LDH protein expression demonstrated a shift by decreasing LDH-B isoforms and increasing LDH-A isoforms. LDH-B activity decreased 80% after 3 days of functional overload. Additionally, LDH-A activity increased by 234% following 3 days of hindlimb suspension. However, neither LDH-A or LDH-B mRNA abundance was affected following 3 days of hindlimb suspension. In summary, the onset of altered loading induced a differential expression of LDH-A and -B in the rat soleus muscle, favoring rapid energy production. Long-term altered loading is associated with myofiber conversion; however, the rapid changes in LDH at the onset of altered loading may be involved in other physiological processes.

  10. Dairy cows affected by ketosis show alterations in innate immunity and lipid and carbohydrate metabolism during the dry off period and postpartum.

    PubMed

    Zhang, Guanshi; Hailemariam, Dagnachew; Dervishi, Elda; Goldansaz, Seyed Ali; Deng, Qilan; Dunn, Suzanna M; Ametaj, Burim N

    2016-08-01

    The objective of this investigation was to search for alterations in blood variables related to innate immunity and carbohydrate and lipid metabolism during the transition period in cows affected by ketosis. One hundred multiparous Holstein dairy cows were involved in the study. Blood samples were collected at -8, -4, week of disease diagnosis (+1 to +3weeks), and +4weeks relative to parturition from 6 healthy cows (CON) and 6 cows with ketosis and were analyzed for serum variables. Results showed that cows with ketosis had greater concentrations of serum β-hydroxybutyric acid (BHBA), interleukin (IL)-6, tumor necrosis factor (TNF), serum amyloid A (SAA), and lactate in comparison with the CON animals. Serum concentrations of BHBA, IL-6, TNF, and lactate were greater starting at -8 and -4weeks prior to parturition in cows with ketosis vs those of CON group. Cows with ketosis also had lower DMI and milk production vs CON cows. Milk fat also was lower in ketotic cows at diagnosis of disease. Cows affected by ketosis showed an activated innate immunity and altered carbohydrate and lipid metabolism several weeks prior to diagnosis of disease. Serum IL-6 and lactate were the strongest discriminators between ketosis cows and CON ones before the occurrence of ketosis, which might be useful as predictive biomarkers of the disease state.

  11. Decreased rate of protein synthesis, caspase-3 activity, and ubiquitin-proteasome proteolysis in soleus muscles from growing rats fed a low-protein, high-carbohydrate diet.

    PubMed

    Batistela, Emanuele; Pereira, Mayara Peron; Siqueira, Juliany Torres; Paula-Gomes, Silvia; Zanon, Neusa Maria; Oliveira, Eduardo Brandt; Navegantes, Luiz Carlos Carvalho; Kettelhut, Isis C; Andrade, Claudia Marlise Balbinotti; Kawashita, Nair Honda; Baviera, Amanda Martins

    2014-06-01

    The aim of this study was to investigate the changes in the rates of both protein synthesis and breakdown, and the activation of intracellular effectors that control these processes in soleus muscles from growing rats fed a low-protein, high-carbohydrate (LPHC) diet for 15 days. The mass and the protein content, as well as the rate of protein synthesis, were decreased in the soleus from LPHC-fed rats. The availability of amino acids was diminished, since the levels of various essential amino acids were decreased in the plasma of LPHC-fed rats. Overall rate of proteolysis was also decreased, explained by reductions in the mRNA levels of atrogin-1 and MuRF-1, ubiquitin conjugates, proteasome activity, and in the activity of caspase-3. Soleus muscles from LPHC-fed rats showed increased insulin sensitivity, with increased levels of insulin receptor and phosphorylation levels of AKT, which probably explains the inhibition of both the caspase-3 activity and the ubiquitin-proteasome system. The fall of muscle proteolysis seems to represent an adaptive response that contributes to spare proteins in a condition of diminished availability of dietary amino acids. Furthermore, the decreased rate of protein synthesis may be the driving factor to the lower muscle mass gain in growing rats fed the LPHC diet.

  12. Pulmonary neuroendocrine cells, airway innervation, and smooth muscle are altered in Cftr null mice.

    PubMed

    Pan, Jie; Luk, Catherine; Kent, Geraldine; Cutz, Ernest; Yeger, Herman

    2006-09-01

    The amine- and peptide-producing pulmonary neuroendocrine cells (PNEC) are widely distributed within the airway mucosa of mammalian lung as solitary cells and innervated clusters, neuroepithelial bodies (NEB), which function as airway O2 sensors. These cells express Cftr and hence could play a role in the pathophysiology of cystic fibrosis (CF) lung disease. We performed confocal microscopy and morphometric analysis on lung sections from Cftr-/- (null), Cftr+/+, and Cftr+/- (control) mice at developmental stages E20, P5, P9, and P30 to determine the distribution, frequency, and innervation of PNEC/NEB, innervation and cell mass of airway smooth muscle, and neuromuscular junctions using synaptic vesicle protein 2, smooth muscle actin, and synaptophysin markers, respectively. The mean number of PNEC/NEB in Cftr-/- mice was significantly reduced compared with control mice at E20, whereas comparable or increased numbers were observed postnatally. NEB cells in Cftr null mice showed a significant reduction in intracorpuscular nerve endings compared with control mice, which is consistent with an intrinsic abnormality of the PNEC system. The airways of Cftr-/- mice showed reduced density (approximately 20-30%) of smooth muscle innervation, decreased mean airway smooth muscle mass (approximately 35%), and reduced density (approximately 20%) of nerve endings compared with control mice. We conclude that the airways of Cftr-/- mice exhibit heretofore unappreciated structural alterations affecting cellular and neural components of the PNEC system and airway smooth muscle and its innervation resulting in blunted O2 sensing and reduced airway tonus. Cftr could play a role in the development of the PNEC system, lung innervation, and airway smooth muscle.

  13. Deconditioning fails to explain peripheral skeletal muscle alterations in men with chronic heart failure.

    PubMed

    Duscha, Brian D; Annex, Brian H; Green, Howard J; Pippen, Anne M; Kraus, William E

    2002-04-03

    It remains controversial whether the skeletal muscle alterations in chronic heart failure (CHF) are due to disease pathophysiology or result from chronic deconditioning. The purpose of this study was to compare the skeletal muscle of CHF patients to peak oxygen consumption (peak VO(2)) matched sedentary controls. It has been established that skeletal muscle abnormalities are related to the exercise intolerance observed in patients with CHF. We studied the skeletal muscle of sedentary controls and patients with CHF matched for age, gender and peak VO(2). Hypothesis testing for the effects of group (CHF vs. normal), gender, and the interaction group x gender were performed. For capillary density only gender (p = 0.002) and the interaction of group x gender (p = 0.007) were significantly different. For 3-hydroxyl coenzyme A (CoA) dehydrogenase only group effect (p = 0.004) was significantly different. Mean values for capillary density were 1.46 +/- 0.28 for CHF men versus 1.87 +/- 0.32 for sedentary control men, 1.40 +/- 0.32 for CHF women versus 1.15 +/- 0.35 for sedentary control women. The activities for 3-hydroxyl CoA dehydrogenase were 3.09 +/- 0.88 for CHF men versus 4.05 +/- 0.42 for sedentary control men, 2.93 +/- 0.72 for CHF women versus 3.51 +/- 0.78 for sedentary control women. This study suggests that women and men adapt to CHF differently: men develop peripheral skeletal muscle abnormalities that are not attributable to deconditioning; women do not develop the same pathologic responses in skeletal muscle when compared with normal women matched for aerobic capacity.

  14. Wearing an Inflatable Vest Alters Muscle Activation and Trunk Angle While Paddling a Surfboard.

    PubMed

    Nessler, Jeff A; Hastings, Thomas; Greer, Kevin; Newcomer, Sean C

    2017-03-02

    Low back pain is a commonly reported problem among recreational surfers. Some individuals report that wearing a vest with an inflatable bladder that alters trunk angle may help to alleviate pain. The purpose of this study was to determine whether such a vest has an effect on muscle activation and extension of the lower back. Twelve recreational surfers completed 12 paddling trials at 1.1 m/s in a swim flume on both a shortboard and a longboard on two separate days. Three conditions of no vest, vest uninflated, and vest inflated were presented to participants in random order. Surface EMG and trunk angle were acquired via wireless sensors placed over the right erector spinae, mid-trapezius, upper trapezius, and latissimus dorsi. Wearing the inflated vest affected muscle activation: erector spinae and mid-trapezius demonstrated a significant decrease in activation relative to wearing no vest (12 and 18% respectively, p<0.05). Trunk extension was also significantly reduced when the vest was inflated (18% reduction, p<0.05). Results were similar for both the short and longboard, though this effect was greater while paddling the larger board. These results suggest that a properly inflated vest can alter trunk extension and muscle activity while paddling a surfboard in water.

  15. Skeletal muscle alterations and exercise performance decrease in erythropoietin-deficient mice: a comparative study

    PubMed Central

    2012-01-01

    Background Erythropoietin (EPO) is known to improve exercise performance by increasing oxygen blood transport and thus inducing a higher maximum oxygen uptake (VO2max). Furthermore, treatment with (or overexpression of) EPO induces protective effects in several tissues, including the myocardium. However, it is not known whether EPO exerts this protective effect when present at physiological levels. Given that EPO receptors have been identified in skeletal muscle, we hypothesized that EPO may have a direct, protective effect on this tissue. Thus, the objectives of the present study were to confirm a decrease in exercise performance and highlight muscle transcriptome alterations in a murine EPO functional knock-out model (the EPO-d mouse). Methods We determined VO2max peak velocity and critical speed in exhaustive runs in 17 mice (9 EPO-d animals and 8 inbred controls), using treadmill enclosed in a metabolic chamber. Mice were sacrificed 24h after a last exhaustive treadmill exercise at critical speed. The tibialis anterior and soleus muscles were removed and total RNA was extracted for microarray gene expression analysis. Results The EPO-d mice’s hematocrit was about 50% lower than that of controls (p < 0.05) and their performance level was about 25% lower (p < 0.001). A total of 1583 genes exhibited significant changes in their expression levels. However, 68 genes were strongly up-regulated (normalized ratio > 1.4) and 115 were strongly down-regulated (normalized ratio < 0.80). The transcriptome data mining analysis showed that the exercise in the EPO-d mice induced muscle hypoxia, oxidative stress and proteolysis associated with energy pathway disruptions in glycolysis and mitochondrial oxidative phosphorylation. Conclusions Our results showed that the lack of functional EPO induced a decrease in the aerobic exercise capacity. This decrease was correlated with the hematocrit and reflecting poor oxygen supply to the muscles. The observed

  16. Effects of Carbohydrate Intake Before and During An Ice Hockey Game on Blood and Muscle Energy Substrates.

    ERIC Educational Resources Information Center

    Simard, Clermont; And Others

    1988-01-01

    Study of the effect of a supplemental carbohydrate intake for seven elite ice hockey players before and during a game demonstrated that the supplement could result in less glycogen usage per distance skated, which had important implications for athletes who may participate in more than one game a day. (Author/CB)

  17. Effects of Carbohydrate Intake Before and During An Ice Hockey Game on Blood and Muscle Energy Substrates.

    ERIC Educational Resources Information Center

    Simard, Clermont; And Others

    1988-01-01

    Study of the effect of a supplemental carbohydrate intake for seven elite ice hockey players before and during a game demonstrated that the supplement could result in less glycogen usage per distance skated, which had important implications for athletes who may participate in more than one game a day. (Author/CB)

  18. Stanniocalcin 1 alters muscle and bone structure and function in transgenic mice.

    PubMed

    Filvaroff, Ellen H; Guillet, Susan; Zlot, Constance; Bao, Min; Ingle, Gladys; Steinmetz, Hope; Hoeffel, John; Bunting, Stuart; Ross, Jed; Carano, Richard A D; Powell-Braxton, Lyn; Wagner, Graham F; Eckert, Renee; Gerritsen, Mary E; French, Dorothy M

    2002-09-01

    Fish stanniocalcin (STC) inhibits uptake of calcium and stimulates phosphate reabsorption. To determine the role of the highly homologous mammalian protein, STC-1, we created and characterized transgenic mice that express STC-1 under control of a muscle-specific promoter. STC-1 transgenic mice were smaller than wild-type littermates and had normal growth plate cartilage morphology but increased cartilage matrix synthesis. In STC-1 mice, the rate of bone formation, but not bone mineralization, was decreased. Increased cortical bone thickness and changes in trabeculae number, density, and thickness in STC-1 mice indicated a concomitant suppression of osteoclast activity, which was supported by microcomputed tomography analyses and histochemistry. Skeletal muscles were disproportionately small and showed altered function and response to injury in STC-1 mice. Electron microscopy indicated that muscle mitochondria were dramatically enlarged in STC-1 mice. These changes in STC-1 mice could not be explained by deficits in blood vessel formation, as vascularity in organs and skeletal tissues was increased as was induction of vascularity in response to femoral artery ligation. Our results indicate that STC-1 can affect calcium homeostasis, bone and muscle mass and structure, and angiogenesis through effects on osteoblasts, osteoclasts, myoblasts/myocytes, and endothelial cells.

  19. Aging-induced alterations in female rat colon smooth muscle: the protective effects of hormonal therapy.

    PubMed

    Pascua, P; Camello-Almaraz, C; Pozo, M J; Martin-Cano, F E; Vara, E; Fernández-Tresguerres, J A; Camello, P J

    2012-06-01

    Aging is associated to oxidative damage and alterations in inflammatory and apoptotic pathways. Aging impairs secretion of several hormones, including melatonin and estrogens. However, the mechanisms involved in aging of smooth muscle are poorly known. We have studied the changes induced by aging in the colonic smooth muscle layer of female rats and the protective effect of hormonal therapy. We used young, aged, and ovariectomized aged female rats. Two groups of ovariectomized rats (22 months old) were treated either with melatonin or with estrogen for 10 weeks before sacrifice. Aging induced oxidative imbalance, evidenced by H(2)O(2) accumulation, lipid peroxidation, and decreased catalase activity. The oxidative damage was enhanced by ovariectomy. In addition, aged colonic muscle showed enhanced expression of the pro-inflammatory enzyme cyclooxygenase 2. Expression of the activated forms of caspases 3 and 9 was also enhanced in aged colon. Melatonin and estrogen treatment prevented the oxidative damage and the activation of caspases. In conclusion, aging of colonic smooth muscle induces oxidative imbalance and activation of apoptotic and pro-inflammatory pathways. Hormonal therapy has beneficial effects on the oxidative and apoptotic changes associated to aging in this model.

  20. (p-ClPhSe)2 stimulates carbohydrate metabolism and reverses the metabolic alterations induced by high fructose load in rats.

    PubMed

    Quines, Caroline B; Rosa, Suzan G; Chagas, Pietro M; Velasquez, Daniela; Prado, Vinicius C; Nogueira, Cristina W

    2017-09-01

    The modern life leads to excess consumption of food rich in fructose; however, the long-term changes in carbohydrate and lipid metabolism could lead to metabolic dysfunction in humans. The present study evaluated the in vitro insulin-mimetic action of p-chloro-diphenyl diselenide (p-ClPhSe)2. The second aim of this study was to investigate if (p-ClPhSe)2 reverses metabolic dysfunction induced by fructose load in Wistar rats. The insulin-mimetic action of (p-ClPhSe)2 at concentrations of 50 and 100 μM was determined in slices of rat skeletal muscle. (p-ClPhSe)2 at a concentration of 50 μM stimulated the glucose uptake by 40% in skeletal muscle. A dose-response curve revealed that (p-ClPhSe)2 at a dose of 25 mg/kg reduced (∼20%) glycemia in rats treated with fructose (5 g/kg, i.g.). The administration of fructose impaired the liver homeostasis and (p-ClPhSe)2 (25 mg/kg) protected against the increase (∼25%) in the G-6-Pase and isocitrate dehydrogenase activities and reduced the triglyceride content (∼25%) in the liver. (p-ClPhSe)2 regulated the liver homeostasis by stimulating hexokinase activity (∼27%), regulating the TCA cycle activity (increased the ATP and citrate synthase activity (∼15%)) and increasing the glycogen levels (∼67%). In conclusion, (p-ClPhSe)2 stimulated carbohydrate metabolism and reversed metabolic dysfunction in rats fed with fructose. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Ultrastructural features of masseter muscle exhibiting altered occlusal relationship—a study in a rodent model

    NASA Astrophysics Data System (ADS)

    Lisboa, Marcio V.; Aciole, Gilberth T. S.; Oliveira, Susana C. P. S.; Marques, Aparecida M. C.; Baptista, Abrahão F.; Pinheiro, Antonio L. B.; Aguiar, Marcio C.; Santos, Jean N.

    2010-05-01

    The role of occlusion on Tempormandibular Disorders (TMD) is still unclear, mainly regarding muscular function. The aim of this study was to evaluate the occlusion highlights on masseter ultra morphology. Twenty Wistar rats were randomly divided in four groups: 10 for control group, 10 for occlusal alteration group (CCO). Rats underwent unilateral amputation of the left inferior and superior molar cusps to simulate an occlusal wear situation. The rats of control group had no occlusal wear. Half of the animals of each group was sacrificed in 14 days after the occlusal consuming and half 30 days after the occlusal consuming. The masseter muscles ipsilateral to the amputated molars were excised and processed for light microscopy, electron microscopy. The light microscopy did not show differences between the groups. The electron microscopy was able to detect a degree of intracellular damage in muscle fibers of CCO group: swollen mitochondria with disrupted cristae and cleared matrix, signs of hypercontraction of I bands and myofibril disorganization.

  2. Altered distribution of mitochondria in rat soleus muscle fibers after spaceflight

    NASA Technical Reports Server (NTRS)

    Bell, Gordon J.; Martin, Thomas P.; Il'ina-Kakueva, E. I.; Oganov, V. S.; Edgerton, V. R.

    1992-01-01

    The effect of an exposure to microgravity on the distribution of the succinate dehydrogenase (SDH) activity throughout the soleus muscle fibers was investigated by measuring SDH activity throughout the cross section of 20-30 fibers each of the slow-twitch oxidative and fast-twitch oxidative-glycolytic types of fibers in rats exposed to 12.5 days in space aboard Cosmos 1887. It was found that, after the spaceflight, the entire regional distribution of SDH activity was significantly altered (as compared to ground controls) in the slow-twitch oxidative fibers, whereas the fast-twitch oxidative-glycolytic fibers from muscles of flown rats exhibited a significantly lower SDH activity only in their subsarcolemmal region.

  3. Ultrastructural features of masseter muscle exhibiting altered occlusal relationship - a study in a rodent model

    SciTech Connect

    Lisboa, Marcio V.; Aciole, Gilberth T. S.; Oliveira, Susana C. P. S.; Marques, Aparecida M. C.; Pinheiro, Antonio L. B.; Santos, Jean N.; Baptista, Abrahao F.; Aguiar, Marcio C.

    2010-05-31

    The role of occlusion on Tempormandibular Disorders (TMD) is still unclear, mainly regarding muscular function. The aim of this study was to evaluate the occlusion highlights on masseter ultra morphology. Twenty Wistar rats were randomly divided in four groups: 10 for control group, 10 for occlusal alteration group (CCO). Rats underwent unilateral amputation of the left inferior and superior molar cusps to simulate an occlusal wear situation. The rats of control group had no occlusal wear. Half of the animals of each group was sacrificed in 14 days after the occlusal consuming and half 30 days after the occlusal consuming. The masseter muscles ipsilateral to the amputated molars were excised and processed for light microscopy, electron microscopy. The light microscopy did not show differences between the groups. The electron microscopy was able to detect a degree of intracellular damage in muscle fibers of CCO group: swollen mitochondria with disrupted cristae and cleared matrix, signs of hypercontraction of I bands and myofibril disorganization.

  4. Altered distribution of mitochondria in rat soleus muscle fibers after spaceflight

    NASA Technical Reports Server (NTRS)

    Bell, Gordon J.; Martin, Thomas P.; Il'ina-Kakueva, E. I.; Oganov, V. S.; Edgerton, V. R.

    1992-01-01

    The effect of an exposure to microgravity on the distribution of the succinate dehydrogenase (SDH) activity throughout the soleus muscle fibers was investigated by measuring SDH activity throughout the cross section of 20-30 fibers each of the slow-twitch oxidative and fast-twitch oxidative-glycolytic types of fibers in rats exposed to 12.5 days in space aboard Cosmos 1887. It was found that, after the spaceflight, the entire regional distribution of SDH activity was significantly altered (as compared to ground controls) in the slow-twitch oxidative fibers, whereas the fast-twitch oxidative-glycolytic fibers from muscles of flown rats exhibited a significantly lower SDH activity only in their subsarcolemmal region.

  5. Alterations of the in vivo torque-velocity relationship of human skeletal muscle following 30 days exposure to simulated microgravity

    NASA Technical Reports Server (NTRS)

    Dudley, Gary A.; Duvoisin, Marc; Convertino, Victor A.; Buchanan, Paul

    1989-01-01

    The effect of a continuous 30-d-long 6-deg headdown bedrest (BR) on the force output ability of skeletal muscles was investigated in human subjects by measuring peak angle specific torque of the knee extensor (KE) and knee flexor (KF) muscle groups of both limbs during unilateral efforts at four speeds (0.52. 1.74, 2.97, and 4.19 rad/sec) during eccentric action. It was found that, for the KE muscle group, the headdown BR resulted in decreases, by 19 percent on the average, of peak angle specific torque; on the other hand, the strength of the KF muscles was not altered significantly. A post-BR recovery for 30 days was found to restore muscle strength of the KE muscle group to about 92 percent of the pre-BR values. Changes of strength were not affected by the type of speed of muscle action.

  6. Alterations of the in vivo torque-velocity relationship of human skeletal muscle following 30 days exposure to simulated microgravity

    NASA Technical Reports Server (NTRS)

    Dudley, Gary A.; Duvoisin, Marc; Convertino, Victor A.; Buchanan, Paul

    1989-01-01

    The effect of a continuous 30-d-long 6-deg headdown bedrest (BR) on the force output ability of skeletal muscles was investigated in human subjects by measuring peak angle specific torque of the knee extensor (KE) and knee flexor (KF) muscle groups of both limbs during unilateral efforts at four speeds (0.52. 1.74, 2.97, and 4.19 rad/sec) during eccentric action. It was found that, for the KE muscle group, the headdown BR resulted in decreases, by 19 percent on the average, of peak angle specific torque; on the other hand, the strength of the KF muscles was not altered significantly. A post-BR recovery for 30 days was found to restore muscle strength of the KE muscle group to about 92 percent of the pre-BR values. Changes of strength were not affected by the type of speed of muscle action.

  7. Antenatal corticosteroids alter insulin signaling pathways in fetal baboon skeletal muscle.

    PubMed

    Blanco, Cynthia L; Moreira, Alvaro G; McGill-Vargas, Lisa L; Anzueto, Diana G; Nathanielsz, Peter; Musi, Nicolas

    2014-05-01

    We hypothesize that prenatal exposure to glucocorticoids (GCs) negatively alters the insulin signal transduction pathway and has differing effects on the fetus according to gestational age (GA) at exposure. Twenty-three fetal baboons were delivered from 23 healthy, nondiabetic mothers. Twelve preterm (0.67 GA) and 11 near-term (0.95 GA) baboons were killed immediately after delivery. Half of the pregnant baboons at each gestation received two doses of i.m. betamethasone 24 h apart (170 μg/kg) before delivery, while the other half received no intervention. Vastus lateralis muscle was obtained from postnatal animals to measure the protein content and gene expression of insulin receptor β (IRβ; INSR), IRβ Tyr 1361 phosphorylation (pIRβ), IR substrate 1 (IRS1), IRS1 tyrosine phosphorylation (pIRS1), p85 subunit of PI3-kinase, AKT (protein kinase B), phospho-AKT Ser473 (pAKT), AKT1, AKT2, and glucose transporters (GLUT1 and GLUT4). Skeletal muscle from preterm baboons exposed to GCs had markedly reduced protein content of AKT and AKT1 (respectively, 73 and 72% from 0.67 GA control, P<0.001); IRβ and pIRβ were also decreased (respectively, 94 and 85%, P<0.01) in the muscle of premature GC-exposed fetuses but not in term fetuses. GLUT1 and GLUT4 tended to increase with GC exposure in preterm animals (P=0.09), while GLUT4 increased sixfold in term animals after exposure to GC (P<0.05). In conclusion, exposure to a single course of antenatal GCs during fetal life alters the insulin signaling pathway in fetal muscle in a manner dependent on the stage of gestation.

  8. Antenatal Corticosteroids Alter Insulin Signaling Pathways in Fetal Baboon Skeletal Muscle

    PubMed Central

    BLANCO, Cynthia L.; MOREIRA, Alvaro G.; McGILL, Lisa L.; ANZUETO, Diana G.; NATHANIELSZ, Peter; MUSI, Nicolas

    2015-01-01

    Objective We hypothesize that prenatal exposure to glucocorticoids (GCs) will negatively alter the insulin signal transduction pathway and has differing effects on the fetus according to gestational age at exposure. Methods Twenty-three fetal baboons were delivered from twenty-three healthy, non-diabetic mothers. Twelve preterm (0.67 gestational age) and eleven near term (0.95 gestational age) baboons were euthanized immediately after delivery. Half of the pregnant baboons at each gestation received two doses of intramuscular betamethasone 24-hours apart (170 μg.kg−1) before delivery, while the other half received no intervention. Vastus lateralis muscle was obtained from postnatal animals to measure protein content and gene expression of insulin receptor (IR)-β, IR-β Tyr 1361 phosphorylation (pIR-β), IR substate-1 (IRS-1), IRS-1 tyrosine phosphorylation (pIRS-1), p85 subunit of PI3-kinase (p85), Akt (Protein Kinase B), phospho-Akt Ser473 (pAkt), Akt-1, Akt-2, and glucose transporters (GLUT1 and GLUT4). Results Skeletal muscle from preterm baboons exposed to glucocorticoids had markedly reduced protein content of Akt and Akt-1 (respectively, 73% and 72% from 0.67 gestational age Control, P<0.001); IR-β and pIR-β were decreased (respectively, 94% and 85%, P<0.01) in the muscle of premature GC exposed fetuses, but not in term fetuses. GLUT1 and GLUT4 tended to increase with GC exposure in preterm animals (P=0.09), while GLUT4 increased 6.0 fold in term animals after GC exposure (P<0.05). Conclusion Exposure to a single course of antenatal GCs during fetal life alters the insulin-signaling pathway in fetal muscle in a manner dependent on the stage of gestation. PMID:24756099

  9. Omega-3 supplementation alters mitochondrial membrane composition and respiration kinetics in human skeletal muscle.

    PubMed

    Herbst, E A F; Paglialunga, S; Gerling, C; Whitfield, J; Mukai, K; Chabowski, A; Heigenhauser, G J F; Spriet, L L; Holloway, G P

    2014-03-15

    Studies have shown increased incorporation of omega-3 fatty acids into whole skeletal muscle following supplementation, although little has been done to investigate the potential impact on the fatty acid composition of mitochondrial membranes and the functional consequences on mitochondrial bioenergetics. Therefore, we supplemented young healthy male subjects (n = 18) with fish oils [2 g eicosapentaenoic acid (EPA) and 1 g docosahexanoic acid (DHA) per day] for 12 weeks and skeletal muscle biopsies were taken prior to (Pre) and following (Post) supplementation for the analysis of mitochondrial membrane phospholipid composition and various assessments of mitochondrial bioenergetics. Total EPA and DHA content in mitochondrial membranes increased (P < 0.05) ∼450 and ∼320%, respectively, and displaced some omega-6 species in several phospholipid populations. Mitochondrial respiration, determined in permeabilized muscle fibres, demonstrated no change in maximal substrate-supported respiration, or in the sensitivity (apparent Km) and maximal capacity for pyruvate-supported respiration. In contrast, mitochondrial responses during ADP titrations demonstrated an enhanced ADP sensitivity (decreased apparent Km) that was independent of the creatine kinase shuttle. As the content of ANT1, ANT2, and subunits of the electron transport chain were unaltered by supplementation, these data suggest that prolonged omega-3 intake improves ADP kinetics in human skeletal muscle mitochondria through alterations in membrane structure and/or post-translational modification of ATP synthase and ANT isoforms. Omega-3 supplementation also increased the capacity for mitochondrial reactive oxygen species emission without altering the content of oxidative products, suggesting the absence of oxidative damage. The current data strongly emphasize a role for omega-3s in reorganizing the composition of mitochondrial membranes while promoting improvements in ADP sensitivity.

  10. Does high-sucrose diet alter skeletal muscle and liver mitochondrial respiration?

    PubMed

    Lambert, K; Py, G; Robert, E; Mercier, J

    2003-09-01

    A diet high in sucrose or fructose progressively impairs glucose and lipid metabolism, which leads to insulin resistance. As mitochondria are the sites of the oxidation and utilization of these substrates, we hypothesized that a high sucrose diet would alter mitochondrial respiration. Male Wistar rats were fed high-sucrose (SU) or control (CTL) diet for one week; mitochondrial respiration was investigated in mitochondria isolated from liver and both glycolytic and oxidative muscles, with pyruvate and palmitate as substrates. To test for metabolic disturbances, we measured not only glycogen content in muscles and liver, but also lactate, glucose and triglyceride blood concentrations. After one week of high-sucrose intake, we found no change in blood concentration of these variables, but glycogen content was significantly increased in liver (17.28 +/- 2.98 mg/g tissue SU vs 6.47 +/- 1.67 mg/g tissue CTL), oxidative muscle (1.59 +/- 0.21 mg/g tissue SU vs 0.70 +/- 0.24 mg/g tissue CTL) though not in glycolytic muscle (1.72 +/- 0.44 mg/g tissue SU vs 1.52 +/- 0.20 mg/g tissue CTL). State 3 mitochondrial respiration was significantly decreased in SU rats compared with CTL (p < 0.05) with pyruvate, while no change was observed with palmitate. This study shows that 1-week of high-sucrose diet altered mitochondrial pyruvate oxidation in rats and suggests that, in the context of a high-sucrose diet, impaired mitochondrial respiration could contributed to the development of insulin resistance.

  11. Seven days of oral taurine supplementation does not increase muscle taurine content or alter substrate metabolism during prolonged exercise in humans.

    PubMed

    Galloway, Stuart D R; Talanian, Jason L; Shoveller, Anna K; Heigenhauser, George J F; Spriet, Lawrence L

    2008-08-01

    This study examined 1) the plasma taurine response to acute oral taurine supplementation (T), and 2) the effects of 7 days of T on muscle amino acid content and substrate metabolism during 2 h of cycling at approximately 60% peak oxygen consumption (VO2peak). In the first part of the study, after an overnight fast, 7 volunteers (28+/-3 yr, 184+/-2 cm, 88.0+/-6.6 kg) ingested 1.66 g oral taurine doses with breakfast (8 AM) and lunch (12 noon), and blood samples were taken throughout the day. In the second part of the study, eight men (22+/-1 yr, 181+/-1 cm, 80.9+/-3.8 kg, 4.21+/-0.16 l/min VO2peak) cycled for 2 h after 7 days of placebo (P) ingestion (6 g glucose/day) and again following 7 days of T (5 g/day). In the first part of the study, plasma taurine was 64+/-4 microM before T and rose rapidly to 778+/-139 microM by 10 AM and remained elevated at noon (359+/-56 microM). Plasma taurine reached 973+/-181 microM at 1 PM and was 161+/-31 microM at 4 PM. In the second part of the study, seven days of T had no effect on muscle taurine content (mmol/kg dry muscle) at rest (P, 44+/-15 vs. T, 42+/-15) or after exercise (P, 43+/-12 vs. T, 43+/-11). There was no difference in muscle glycogen or other muscle metabolites between conditions, but there were notable interaction effects for muscle valine, isoleucine, leucine, cystine, glutamate, alanine, and arginine amino acid content following exercise after T. These data indicate that 1) acute T produces a 13-fold increase in plasma taurine concentration; 2) despite the ability to significantly elevate plasma taurine for extended periods throughout the day, 7 days of T does not alter skeletal muscle taurine content or carbohydrate and fat oxidation during exercise; and 3) T appears to have some impact on muscle amino acid response to exercise.

  12. Musculoskeletal Sensitization and Sleep: Chronic Muscle Pain Fragments Sleep of Mice without Altering Its Duration

    PubMed Central

    Sutton, Blair C.; Opp, Mark R.

    2014-01-01

    Study Objectives: Musculoskeletal pain in humans is often associated with poor sleep quality. We used a model in which mechanical hypersensitivity was induced by injection of acidified saline into muscle to study the impact of musculoskeletal sensitization on sleep of mice. Design: A one month pre-clinical study was designed to determine the impact of musculoskeletal sensitization on sleep of C57BL/6J mice. Methods: We instrumented mice with telemeters to record the electroencephalogram (EEG) and body temperature. We used an established model of musculoskeletal sensitization in which mechanical hypersensitivity was induced using two unilateral injections of acidified saline (pH 4.0). The injections were given into the gastrocnemius muscle and spaced five days apart. EEG and body temperature recordings started prior to injections (baseline) and continued for three weeks after musculoskeletal sensitization was induced by the second injection. Mechanical hypersensitivity was assessed using von Frey filaments at baseline (before any injections) and on days 1, 3, 7, 14, and 21 after the second injection. Results: Mice injected with acidified saline developed bilateral mechanical hypersensitivity at the hind paws as measured by von Frey testing and as compared to control mice and baseline data. Sleep during the light period was fragmented in experimental mice injected with acidified saline, and EEG spectra altered. Musculoskeletal sensitization did not alter the duration of time spent in wakefulness, non-rapid eye movement sleep, or rapid eye movement sleep. Conclusions: Musculoskeletal sensitization in this model results in a distinct sleep phenotype in which sleep is fragmented during the light period, but the overall duration of sleep is not changed. This study suggests the consequences of musculoskeletal pain include sleep disruption, an observation that has been made in the clinical literature but has yet to be studied using preclinical models. Citation: Sutton BC

  13. P2X7 purinoceptor alterations in dystrophic mdx mouse muscles: relationship to pathology and potential target for treatment.

    PubMed

    Young, Christopher N J; Brutkowski, Wojciech; Lien, Chun-Fu; Arkle, Stephen; Lochmüller, Hanns; Zabłocki, Krzysztof; Górecki, Dariusz C

    2012-05-01

    Duchenne muscular dystrophy (DMD) is a lethal inherited muscle disorder. Pathological characteristics of DMD skeletal muscles include, among others, abnormal Ca(2+) homeostasis and cell signalling. Here, in the mdx mouse model of DMD, we demonstrate significant P2X7 receptor abnormalities in isolated primary muscle cells and cell lines and in dystrophic muscles in vivo. P2X7 mRNA expression in dystrophic muscles was significantly up-regulated but without alterations of specific splice variant patterns. P2X7 protein was also up-regulated and this was associated with altered function of P2X7 receptors producing increased responsiveness of cytoplasmic Ca(2+) and extracellular signal-regulated kinase (ERK) phosphorylation to purinergic stimulation and altered sensitivity to NAD. Ca(2+) influx and ERK signalling were stimulated by ATP and BzATP, inhibited by specific P2X7 antagonists and insensitive to ivermectin, confirming P2X7 receptor involvement. Despite the presence of pannexin-1, prolonged P2X7 activation did not trigger cell permeabilization to propidium iodide or Lucifer yellow. In dystrophic mice, in vivo treatment with the P2X7 antagonist Coomassie Brilliant Blue reduced the number of degeneration-regeneration cycles in mdx skeletal muscles. Altered P2X7 expression and function is thus an important feature in dystrophic mdx muscle and treatments aiming to inhibit P2X7 receptor might slow the progression of this disease.

  14. The Invalidation of HspB1 Gene in Mouse Alters the Ultrastructural Phenotype of Muscles

    PubMed Central

    Kammoun, Malek; Picard, Brigitte; Astruc, Thierry; Gagaoua, Mohammed; Aubert, Denise; Bonnet, Muriel; Blanquet, Véronique; Cassar-Malek, Isabelle

    2016-01-01

    Even though abundance of Hsp27 is the highest in skeletal muscle, the relationships between the expression of HspB1 (encoding Hsp27) and muscle characteristics are not fully understood. In this study, we have analysed the effect of Hsp27 inactivation on mouse development and phenotype. We generated a mouse strain devoid of Hsp27 protein by homologous recombination of the HspB1 gene. The HspB1-/- mouse was viable and fertile, showing neither apparent morphological nor anatomical alterations. We detected a gender dimorphism with marked effects in males, a lower body weight (P < 0.05) with no obvious changes in the growth rate, and a lower plasma lipids profile (cholesterol, HDL and triglycerides, 0.001 < P< 0.05). The muscle structure of the animals was examined by optical microscopy and transmission electron microscopy. Not any differences in the characteristics of muscle fibres (contractile and metabolic type, shape, perimeter, cross-sectional area) were detected except a trend for a higher proportion of small fibres. Different myosin heavy chains electrophoretic profiles were observed in the HspB1-/- mouse especially the presence of an additional isoform. Electron microscopy revealed ultrastructural abnormalities in the myofibrillar structure of the HspB1-/- mouse mutant mice (e.g. destructured myofibrils and higher gaps between myofibrils) especially in the m. Soleus. Combined with our previous data, these findings suggest that Hsp27 could directly impact the organization of muscle cytoskeleton at the molecular and ultrastructural levels. PMID:27512988

  15. Scapular bracing and alteration of posture and muscle activity in overhead athletes with poor posture.

    PubMed

    Cole, Ashley K; McGrath, Melanie L; Harrington, Shana E; Padua, Darin A; Rucinski, Terri J; Prentice, William E

    2013-01-01

    Overhead athletes commonly have poor posture. Commercial braces are used to improve posture and function, but few researchers have examined the effects of shoulder or scapular bracing on posture and scapular muscle activity. To examine whether a scapular stabilization brace acutely alters posture and scapular muscle activity in healthy overhead athletes with forward-head, rounded-shoulder posture (FHRSP). Randomized controlled clinical trial. Applied biomechanics laboratory. Thirty-eight healthy overhead athletes with FHRSP. Participants were assigned randomly to 2 groups: compression shirt with no strap tension (S) and compression shirt with the straps fully tensioned (S + T). Posture was measured using lateral-view photography with retroreflective markers. Electromyography (EMG) of the upper trapezius (UT), middle trapezius (MT), lower trapezius (LT), and serratus anterior (SA) in the dominant upper extremity was measured during 4 exercises (scapular punches, W's, Y's, T's) and 2 glenohumeral motions (forward flexion, shoulder extension). Posture and exercise EMG measurements were taken with and without the brace applied. Head and shoulder angles were measured from lateral-view digital photographs. Normalized surface EMG was used to assess mean muscle activation of the UT, MT, LT, and SA. Application of the brace decreased forward shoulder angle in the S + T condition. Brace application also caused a small increase in LT EMG during forward flexion and Y's and a small decrease in UT and MT EMG during shoulder extension. Brace application in the S + T group decreased UT EMG during W's, whereas UT EMG increased during W's in the S group. Application of the scapular brace improved shoulder posture and scapular muscle activity, but EMG changes were highly variable. Use of a scapular brace might improve shoulder posture and muscle activity in overhead athletes with poor posture.

  16. Visual scapular dyskinesis: kinematics and muscle activity alterations in patients with subacromial impingement syndrome.

    PubMed

    Lopes, Andrea Diniz; Timmons, Mark K; Grover, Molly; Ciconelli, Rozana Mesquita; Michener, Lori A

    2015-02-01

    To characterize scapular kinematics and shoulder muscle activity in patients with subacromial impingement syndrome, with and without visually identified scapular dyskinesis. Cross-sectional study. Laboratory. Participants with subacromial impingement syndrome (N=38) were visually classified using a scapular dyskinesis test with obvious scapular dyskinesis (n=19) or normal scapular motion (n=19). Not applicable. An electromagnetic motion capture system measured 3-dimensional kinematics of the thorax, humerus, and scapula. Simultaneously, surface electromyography was used to measure muscle activity of the upper, middle, and lower trapezius; serratus anterior; and infraspinatus during ascending and descending phases of weighted shoulder flexion. Separate mixed-model analyses of variance for the ascending and descending phases of shoulder flexion compared kinematics and muscle activity between the 2 groups. Shoulder disability was assessed with the Pennsylvania Shoulder Score (Penn). The group with obvious dyskinesis reported 6 points lower on Penn shoulder function (0-60 points), exhibited a main group effect of less scapular external rotation of 2.1° during ascent and 2.5° during descent, and had 12.0% higher upper trapezius muscle activity during ascent in the 30° to 60° interval. Patients with obvious dyskinesis and subacromial impingement syndrome have reduced scapular external rotation and increased upper trapezius muscle activity, along with a greater loss of shoulder function compared with those without dyskinesis. These biomechanical alterations can lead to or be caused by scapular dyskinesis. Future studies should determine if correction of these deficits will eliminate scapular dyskinesis and improve patient-rated shoulder use. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  17. Radiofrequency ablation near the bone-muscle interface alters soft tissue lesion dimensions.

    PubMed

    Eckmann, Maxim S; Martinez, Marte A; Lindauer, Steven; Khan, Asif; Ramamurthy, Somayaji

    2015-01-01

    Radiofrequency (RF) lesions are safe and effective in the treatment of spine pain; however, models developed to study factors affecting lesion dimensions have been performed in homogeneous media that may not accurately simulate human anatomy and electrophysiology. We present a novel ex vivo porcine model for performing RF lesion studies and report the influence of bone on projection of RF ablation lesions into soft tissue. Radiofrequency lesions were performed in porcine rib specimens using monopolar 18-gauge, 10-mm straight active tip cannula, with a lesion temperature of 80°C for 150 seconds. Ten lesions were performed in pure porcine muscle tissue and abutting porcine rib bone with surrounding muscle. Lesions were exposed with dissection and measured with digital calipers. Maximal effective lesion radius approximately doubled against the bone compared with the pure muscle group (mean, 5.65 mm [95% CI, 5.43-5.87 mm] vs 2.68 mm [95% CI, 2.55-2.81 mm], P < .0001), although this was seen only in a vertical direction and not horizontally. In addition, the prelesion and postlesion impedance of the bone-muscle interface was consistently higher than the muscle-only interface (mean, 165.6 Ohm [95% CI, 146.6-184.6 Ohm] vs 137.8 Ohm [95% CI, 135.5-140.1 Ohm], P = 0.004; 144.3 Ohm [95% CI, 134.3-154.3 Ohm] vs 124.3 Ohm [95% CI, 119.3-129.3 Ohm], P = 0.001). Other dimensions and estimated volume were not significantly different. Bone adjacent to RF lesions alters the surrounding electrophysiological environment causing RF lesions to project further perpendicularly from the needle axis, vertically to bone, than previously expected. This phenomenon should be considered in the future modeling and clinical practice of RF.

  18. Scapular Bracing and Alteration of Posture and Muscle Activity in Overhead Athletes With Poor Posture

    PubMed Central

    Cole, Ashley K; McGrath, Melanie L; Harrington, Shana E; Padua, Darin A; Rucinski, Terri J; Prentice, William E

    2013-01-01

    Context Overhead athletes commonly have poor posture. Commercial braces are used to improve posture and function, but few researchers have examined the effects of shoulder or scapular bracing on posture and scapular muscle activity. Objective To examine whether a scapular stabilization brace acutely alters posture and scapular muscle activity in healthy overhead athletes with forward-head, rounded-shoulder posture (FHRSP). Design Randomized controlled clinical trial. Setting Applied biomechanics laboratory. Patients or Other Participants Thirty-eight healthy overhead athletes with FHRSP. Intervention(s) Participants were assigned randomly to 2 groups: compression shirt with no strap tension (S) and compression shirt with the straps fully tensioned (S + T). Posture was measured using lateral-view photography with retroreflective markers. Electromyography (EMG) of the upper trapezius (UT), middle trapezius (MT), lower trapezius (LT), and serratus anterior (SA) in the dominant upper extremity was measured during 4 exercises (scapular punches, W's, Y's, T's) and 2 glenohumeral motions (forward flexion, shoulder extension). Posture and exercise EMG measurements were taken with and without the brace applied. Main Outcome Measure(s) Head and shoulder angles were measured from lateral-view digital photographs. Normalized surface EMG was used to assess mean muscle activation of the UT, MT, LT, and SA. Results Application of the brace decreased forward shoulder angle in the S + T condition. Brace application also caused a small increase in LT EMG during forward flexion and Y's and a small decrease in UT and MT EMG during shoulder extension. Brace application in the S + T group decreased UT EMG during W's, whereas UT EMG increased during W's in the S group. Conclusions Application of the scapular brace improved shoulder posture and scapular muscle activity, but EMG changes were highly variable. Use of a scapular brace might improve shoulder posture and muscle activity in

  19. Effect of dietary nonstructural carbohydrate content on activation of 5'-adenosine monophosphate-activated protein kinase in liver, skeletal muscle, and digital laminae of lean and obese ponies.

    PubMed

    Burns, T A; Watts, M R; Weber, P S; McCutcheon, L J; Geor, R J; Belknap, J K

    2014-01-01

    In EMS-associated laminitis, laminar failure may occur in response to energy failure related to insulin resistance (IR) or to the effect of hyperinsulinemia on laminar tissue. 5'-Adenosine-monophosphate-activated protein kinase (AMPK) is a marker of tissue energy deprivation, which may occur in IR. To characterize tissue AMPK regulation in ponies subjected to a dietary carbohydrate (CHO) challenge. Twenty-two mixed-breed ponies. Immunohistochemistry and immunoblotting for total AMPK and phospho(P)-AMPK and RT-qPCR for AMPK-responsive genes were performed on laminar, liver, and skeletal muscle samples collected after a 7-day feeding protocol in which ponies stratified on body condition score (BCS; obese or lean) were fed either a low-CHO diet (ESC + starch, approximately 7% DM; n = 5 obese, 5 lean) or a high-CHO diet (ESC + starch, approximately 42% DM; n = 6 obese, 6 lean). 5'-Adenosine-monophosphate-activated protein kinase was immunolocalized to laminar keratinocytes, dermal constituents, and hepatocytes. A high-CHO diet resulted in significantly decreased laminar [P-AMPK] in lean ponies (P = .03), but no changes in skeletal muscle (lean, P = .33; obese, P = .43) or liver (lean, P = .84; obese, P = .13) [P-AMPK]. An inverse correlation existed between [blood glucose] and laminar [P-AMPK] in obese ponies on a high-CHO diet. Laminar tissue exhibited a normal response to a high-CHO diet (decreased [P-AMPK]), whereas this response was not observed in liver and skeletal muscle in both lean (skeletal muscle, P = .33; liver, P = .84) and obese (skeletal muscle, P = .43; liver, P = .13) ponies. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  20. The impact of altered task mechanics on timing and duration of eccentric bi-articular muscle contractions during cycling.

    PubMed

    Connick, Mark J; Li, François-Xavier

    2013-02-01

    In order to understand muscle adaptations to altered task mechanics during cycling, this study investigated the impact of altered seat height and cadence on timing and duration of gastrocnemius (GAST), biceps femoris (BF) and vastus lateralis (VL) eccentric contractions and muscle activation patterns, and cycling economy. Ten male cyclists completed 9 × 5 min of cycling at 3 seat heights and 3 cadences. Three-dimensional leg kinematics and muscle activation patterns were recorded to estimate timing of eccentric muscle contractions. Onset, offset and duration of eccentric contractions and, onset, offset and duration of muscle activation were calculated, along with cycling economy. Duration of GAST and VL eccentric contractions decreased with increasing seat height due to earlier offset of eccentric muscle contractions. Duration of BF eccentric contractions significantly increased with seat height due to a later eccentric contraction offset. Offset of GAST and BF muscle activation occurred earlier with increasing cadence. Cycling economy was significantly affected by cadence but not seat height. The results suggest that as a consequence of altered seat height, proprioceptive feedback is used to fine-tune the timing of bi-articular eccentric muscle contractions. These results may have implications for seat height self-selection.

  1. High-protein-low-carbohydrate diet during pregnancy alters maternal plasma amino acid concentration and placental amino acid extraction but not fetal plasma amino acids in pigs.

    PubMed

    Metzler-Zebeli, Barbara U; Lang, Iris S; Görs, Solvig; Brüssow, Klaus-Peter; Hennig, Ulf; Nürnberg, Gerd; Rehfeldt, Charlotte; Otten, Winfried; Metges, Cornelia C

    2012-12-28

    A high protein-low-carbohydrate diet during pregnancy can cause intra-uterine growth restriction. However, its impact during pregnancy on maternal, umbilical and fetal plasma amino acid (AA) profiles is unknown. A maternal high-protein (30 %)-low-carbohydrate (HP-LC) diet was compared with isoenergetic standard (12·1 % crude protein; ST) and low-protein (6·5 %)-high-carbohydrate (LP-HC) diets fed to nulliparous pregnant sows to examine changes in AA concentrations in maternal, venous and arterial umbilical and fetal plasma in mid and late pregnancy. At 64 and 94 days of pregnancy (dp), sows underwent Caesarean section, and maternal, umbilical and fetal plasma samples were collected. The HP-LC diet mainly affected maternal plasma AA concentrations. Plasma concentrations of Ile and Val were increased and those of Ala, Glu and Gly were decreased (P ≤ 0·05) in HP-LC compared with ST sows at 64 and 94 dp. The LP-HC diet decreased fetal plasma Glu concentration compared with the ST diet at 94 dp. Substantial AA catabolism was reflected by increased (P ≤ 0·05) maternal and fetal plasma urea concentrations with the HP-LC compared with the ST and LP-HC diets at 94 dp. Fractional placental extraction of Val was higher whereas those of Ala, Gln and Glu were lower in the HP-LC compared with the ST sows at 64 and 94 dp (P ≤ 0·05). Reduced fetal mass at 94 dp was accompanied by reduced fetal extraction of Lys and Pro in the HP-LC group (P ≤ 0·05). In conclusion, a maternal HP-LC diet during pregnancy altered maternal plasma composition of many AA and modified placental AA extraction to compensate for imbalanced maternal nutrient intake.

  2. Chronic stress effects in contralateral medial pterygoid muscle of rats with occlusion alteration.

    PubMed

    Loyola, Bruno Melo; Nascimento, Glauce Crivelaro; Fernández, Rodrigo Alberto Restrepo; Iyomasa, Daniela Mizusaki; Pereira, Yamba Carla Lara; Leite-Panissi, Christie Ramos Andrade; Issa, João Paulo Mardegan; Iyomasa, Mamie Mizusaki

    2016-10-01

    +US groups, the deeply stained fibers increased compared to NO+C.·The exodontia factor was able to increase the ROS activity in muscle, whereas the stress factor does not significantly alter ROS in this tissue. It was concluded that both unpredictable chronic stress and the extraction induce metabolic and density of capillary changes in the contralateral medial pterygoid muscle to extraction, suggesting that these factors for a longer period of this experiment could induce muscle damage related to TMD. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Alterations in Carbohydrate Intermediates in the Endosperm of Starch-Deficient Maize (Zea mays L.) Genotypes 1

    PubMed Central

    Tobias, Rowel B.; Boyer, Charles D.; Shannon, Jack C.

    1992-01-01

    Metabolite levels in kernels of selected starch-deficient mutants of maize (Zea mays L.) were investigated to gain insight into partitioning of carbohydrate metabolism during kernel development. Several free sugars, hexose phosphates, triose phosphates, fructose-2,6-bisphosphate, and pyrophosphate were measured in normal, shrunken, shrunken-2, amylose extender dull waxy, and brittle genotypes, which were in a near-isogenic W64A background. These mutants were selected to include at least one lesion in both the cytosolic (shrunken) and amyloplastic (shrunken-2) compartments. All the starch-deficient genotypes contained elevated levels of fructose-2,6-bisphosphate and triose phosphates but reduced levels of pyrophosphate, indicating an enhanced glycolytic utilization of carbohydrates in response to the reduced utilization of sugars for starch synthesis. The shrunken kernels (sucrose synthase deficient) contained reduced levels of glucose-1-phosphate, glucose-6-phosphate, and fructose-6-phosphate, and this reduction paralleled the reduction in starch accumulation, but levels of triose phosphates were elevated. In shrunken-2 kernels, glucose-1-phosphate, glucose-6-phosphate, and fructose-6-phosphate, dihydroxyacetone phosphate, and glyceraldehyde-3-phosphate were increased, but fructose-1,6-bisphosphate was lower. These findings support the view that hexose phosphate transport across the amyloplast envelope is more important for starch biosynthesis than transport of triose phosphates. The amylose extender dull waxy mutation showed less dramatic effects on hexose phosphates, but the triose phosphates were greatly increased. The brittle mutation, which has an unknown lesion, showed distinctly similar changes in metabolite levels with shrunken-2, suggesting that the lesion may be associated with the amyloplast. ImagesFigure 1 PMID:16668842

  4. Alteration of carbohydrates metabolism and midgut glucose absorption in Gromphadorhina portentosa after subchronic exposure to imidacloprid and fenitrothion.

    PubMed

    Sawczyn, Tomasz; Dolezych, Bogdan; Klosok, Marcin; Augustyniak, Maria; Stygar, Dominika; Buldak, Rafal J; Kukla, Michal; Michalczyk, Katarzyna; Karcz-Socha, Iwona; Zwirska-Korczala, Krystyna

    2012-01-01

    This study was undertaken to test the hypothesis that following exposure to insecticides, changes take place in the metabolism of carbohydrates and absorption in the midgut of insects. The Madagascar hissing cockroach (Gromphadorhina portentosa) was chosen for the experiment as a model organism, due to it being easy to breed and its relatively large alimentary tract, which was important when preparing the microperfusion midgut bioassay. In each group of cockroaches treated with imidacloprid and fenitrothion, absorption of glucose, expressed as the area under the curve (AUC), was elevated compared to the control group. Glucose in the hemolymph of the examined insects was present in a vestigial amount, often below the threshold of determination, so the determinable carbohydrate indices were: hemolymph trehalose concentration and fat body glycogen content. The level of trehalose found in the hemolymph of insects when exposed to fenitrothion, and irrespective of the level of concentration mixed into food, were significantly lower when comparing to the control samples. Imidacloprid acted analogically with one exception at the concentration of 10 mg·kg(-1) dry food where trehalose concentration did not differ from the control values. Coupling with fat body glycogen concentration was less visible and appeared only at the concentrations of 5 and 10 mg imidacloprid·kg(-1) dry food. As described in this study changes in the sugar distribution and midgut glucose absorption indicate that insects cover the increased energy needs induced by insecticides; also at the gastrointestinal tract level. The result indicates that the midgut glucose absorption parameters could be considered as a non-specific biomarker of insecticide toxicity.

  5. Transcriptional Signature of an Altered Purine Metabolism in the Skeletal Muscle of a Huntington's Disease Mouse Model

    PubMed Central

    Mielcarek, Michal; Smolenski, Ryszard T.; Isalan, Mark

    2017-01-01

    Huntington's disease (HD) is a fatal neurodegenerative disorder, caused by a polyglutamine expansion in the huntingtin protein (HTT). HD has a peripheral component to its pathology: skeletal muscles are severely affected, leading to atrophy, and malfunction in both pre-clinical and clinical settings. We previously used two symptomatic HD mouse models to demonstrate the impairment of the contractile characteristics of the hind limb muscles, which was accompanied by a significant loss of function of motor units. The mice displayed a significant reduction in muscle force, likely because of deteriorations in energy metabolism, decreased oxidation, and altered purine metabolism. There is growing evidence suggesting that HD-related skeletal muscle malfunction might be partially or completely independent of CNS degeneration. The pathology might arise from mutant HTT within muscle (loss or gain of function). Hence, it is vital to identify novel peripheral biomarkers that will reflect HD skeletal muscle atrophy. These will be important for upcoming clinical trials that may target HD peripherally. In order to identify potential biomarkers that might reflect muscle metabolic changes, we used qPCR to validate key gene transcripts in different skeletal muscle types. Consequently, we report a number of transcript alterations that are linked to HD muscle pathology. PMID:28303108

  6. Loss of IL-15 receptor α alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles.

    PubMed

    Pistilli, Emidio E; Bogdanovich, Sasha; Garton, Fleur; Yang, Nan; Gulbin, Jason P; Conner, Jennifer D; Anderson, Barbara G; Quinn, LeBris S; North, Kathryn; Ahima, Rexford S; Khurana, Tejvir S

    2011-08-01

    IL-15 receptor α (IL-15Rα) is a component of the heterotrimeric plasma membrane receptor for the pleiotropic cytokine IL-15. However, IL-15Rα is not merely an IL-15 receptor subunit, as mice lacking either IL-15 or IL-15Rα have unique phenotypes. IL-15 and IL-15Rα have been implicated in muscle phenotypes, but a role in muscle physiology has not been defined. Here, we have shown that loss of IL-15Rα induces a functional oxidative shift in fast muscles, substantially increasing fatigue resistance and exercise capacity. IL-15Rα-knockout (IL-15Rα-KO) mice ran greater distances and had greater ambulatory activity than controls. Fast muscles displayed fatigue resistance and a slower contractile phenotype. The molecular signature of these muscles included altered markers of mitochondrial biogenesis and calcium homeostasis. Morphologically, fast muscles had a greater number of muscle fibers, smaller fiber areas, and a greater ratio of nuclei to fiber area. The alterations of physiological properties and increased resistance to fatigue in fast muscles are consistent with a shift toward a slower, more oxidative phenotype. Consistent with a conserved functional role in humans, a genetic association was found between a SNP in the IL15RA gene and endurance in athletes stratified by sport. Therefore, we propose that IL-15Rα has a role in defining the phenotype of fast skeletal muscles in vivo.

  7. Loss of IL-15 receptor α alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles

    PubMed Central

    Pistilli, Emidio E.; Bogdanovich, Sasha; Garton, Fleur; Yang, Nan; Gulbin, Jason P.; Conner, Jennifer D.; Anderson, Barbara G.; Quinn, LeBris S.; North, Kathryn; Ahima, Rexford S.; Khurana, Tejvir S.

    2011-01-01

    IL-15 receptor α (IL-15Rα) is a component of the heterotrimeric plasma membrane receptor for the pleiotropic cytokine IL-15. However, IL-15Rα is not merely an IL-15 receptor subunit, as mice lacking either IL-15 or IL-15Rα have unique phenotypes. IL-15 and IL-15Rα have been implicated in muscle phenotypes, but a role in muscle physiology has not been defined. Here, we have shown that loss of IL-15Rα induces a functional oxidative shift in fast muscles, substantially increasing fatigue resistance and exercise capacity. IL-15Rα–knockout (IL-15Rα–KO) mice ran greater distances and had greater ambulatory activity than controls. Fast muscles displayed fatigue resistance and a slower contractile phenotype. The molecular signature of these muscles included altered markers of mitochondrial biogenesis and calcium homeostasis. Morphologically, fast muscles had a greater number of muscle fibers, smaller fiber areas, and a greater ratio of nuclei to fiber area. The alterations of physiological properties and increased resistance to fatigue in fast muscles are consistent with a shift toward a slower, more oxidative phenotype. Consistent with a conserved functional role in humans, a genetic association was found between a SNP in the IL15RA gene and endurance in athletes stratified by sport. Therefore, we propose that IL-15Rα has a role in defining the phenotype of fast skeletal muscles in vivo. PMID:21765213

  8. Expression of a Dominant Negative CELF Protein In Vivo Leads to Altered Muscle Organization, Fiber Size, and Subtype

    PubMed Central

    Berger, Dara S.; Moyer, Michelle; Kliment, Gregory M.; van Lunteren, Erik; Ladd, Andrea N.

    2011-01-01

    Background CUG-BP and ETR-3-like factor (CELF) proteins regulate tissue- and developmental stage-specific alternative splicing in striated muscle. We previously demonstrated that heart muscle-specific expression of a nuclear dominant negative CELF protein in transgenic mice (MHC-CELFΔ) effectively disrupts endogenous CELF activity in the heart in vivo, resulting in impaired cardiac function. In this study, transgenic mice that express the dominant negative protein under a skeletal muscle-specific promoter (Myo-CELFΔ) were generated to investigate the role of CELF-mediated alternative splicing programs in normal skeletal muscle. Methodology/Principal Findings Myo-CELFΔ mice exhibit modest changes in CELF-mediated alternative splicing in skeletal muscle, accompanied by a reduction of endomysial and perimysial spaces, an increase in fiber size variability, and an increase in slow twitch muscle fibers. Weight gain and mean body weight, total number of muscle fibers, and overall muscle strength were not affected. Conclusions/Significance Although these findings demonstrate that CELF activity contributes to the normal alternative splicing of a subset of muscle transcripts in vivo, the mildness of the effects in Myo-CELFΔ muscles compared to those in MHC-CELFΔ hearts suggests CELF activity may be less determinative for alternative splicing in skeletal muscle than in heart muscle. Nonetheless, even these small changes in CELF-mediated splicing regulation were sufficient to alter muscle organization and muscle fiber properties affected in myotonic dystrophy. This lends further evidence to the hypothesis that dysregulation of CELF-mediated alternative splicing programs may be responsible for the disruption of these properties during muscle pathogenesis. PMID:21541285

  9. Responses of Electromyogram Activity in Adductor Longus Muscle of Rats to the Altered Gravity Levels

    NASA Astrophysics Data System (ADS)

    Ohira, Takashi; Wang, Xiao Dong; Terada, Masahiro; Kawano, Fuminori; Higo, Yoko; Nakai, Naoya; Ochiai, Toshimasa; Gyotoku, Jyunichirou; Nishimoto, Norihiro; Ogura, Akihiko; Ohira, Yoshinobu

    2008-06-01

    Responses of electromyogram (EMG) activities in the rostral and caudal regions of adductor longus (AL) muscle to altered gravity levels during parabolic flight of a jet airplane, as well as hindlimb suspension, were investigated in adult rats. Tonic EMGs in both regions were noted when the rats were exposed to hyper-G, as well as 1-G. The hip joints were adducted and the sedental quadrupedal position was maintained at these G levels. However, the EMG activities in these regions decreased and became phasic, when the hip joints were abducted and extended backward in μ-G environment. Such changes of joint angles caused passive shortening of sarcomeres only in the caudal region of AL. Atrophy and shift toward fast-twitch type were noted in fibers of the caudal region after 16-day unloading. Although fiber transformation was also induced in the rostral region, no atrophy was seen in fast-twitch fibers. The data may suggest that the atrophy and shift of phenotype caused by gravitational unloading in fibers of the caudal region may be related to the decrease in the neural and mechanical activities. Fiber type transformation toward fast-twitch type may be also related to the change of muscle activity from tonic to phasic patterns, which are the typical characteristics of fast-twitch muscle. However, the responses to unloading in fibers of rostral region were not related to the reduction of mechanical load.

  10. Maternal High Fat Diet Alters Skeletal Muscle Mitochondrial Catalytic Activity in Adult Male Rat Offspring

    PubMed Central

    Pileggi, Chantal A.; Hedges, Christopher P.; Segovia, Stephanie A.; Markworth, James F.; Durainayagam, Brenan R.; Gray, Clint; Zhang, Xiaoyuan D.; Barnett, Matthew P. G.; Vickers, Mark H.; Hickey, Anthony J. R.; Reynolds, Clare M.; Cameron-Smith, David

    2016-01-01

    A maternal high-fat (HF) diet during pregnancy can lead to metabolic compromise, such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for 10 days prior to mating, throughout pregnancy and during lactation. From weaning, all male offspring received a standard chow diet and soleus muscle was collected at day 150. Expression of the mitochondrial transcription factors nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (mtTFA) were downregulated in HF offspring. Furthermore, genes encoding the mitochondrial electron transport system (ETS) respiratory complex subunits were suppressed in HF offspring. Moreover, protein expression of the complex I subunit, NDUFB8, was downregulated in HF offspring (36%), which was paralleled by decreased maximal catalytic linked activity of complex I and III (40%). Together, these results indicate that exposure to a maternal HF diet during development may elicit lifelong mitochondrial alterations in offspring skeletal muscle. PMID:27917127

  11. Chronic sleep deprivation alters the myosin heavy chain isoforms in the masseter muscle in rats.

    PubMed

    Cao, Ruihua; Huang, Fei; Wang, Peihuan; Chen, Chen; Zhu, Guoxiong; Chen, Lei; Wu, Gaoyi

    2015-05-01

    To investigate the changes in myosin heavy chain (MyHC) isoforms of rat masseter muscle fibres caused by chronic sleep deprivation and a possible link with the pathogenesis of disorders of the temporomandibular joint (TMJ). A total of 180 male rats were randomly divided into three groups (n=60 in each): cage controls, large platform controls, and chronic sleep deprivation group. Each group was further divided into three subgroups with different observation periods (7, 14, and 21 days). We investigated he expression of MyHC isoforms in masseter muscle fibres by real-time quantitative polymerase chain reaction (PCR), Western blotting, and immunohistochemical staining. In rats with chronic sleep deprivation there was increased MyHC-I expression in layers of both shallow and deep muscles at 7 and 21 days compared with the control groups, whereas sleep deprivation was associated with significantly decreased MyHC-II expression. At 21 days, there were no differences in MyHC-I or MyHC-II expression between the groups and there were no differences between the two control groups at any time point. These findings suggest that chronic sleep deprivation alters the expression of MyHC isoforms, which may contribute to the pathogenesis of disorders of the TMJ.

  12. Alterations in zebrafish development induced by simvastatin: Comprehensive morphological and physiological study, focusing on muscle.

    PubMed

    Campos, Laise M; Rios, Eduardo A; Guapyassu, Livia; Midlej, Victor; Atella, Georgia C; Herculano-Houzel, Suzana; Benchimol, Marlene; Mermelstein, Claudia; Costa, Manoel L

    2016-11-01

    The cholesterol synthesis inhibitor simvastatin, which is used to treat cardiovascular diseases, has severe collateral effects. We decided to comprehensively study the effects of simvastatin in zebrafish development and in myogenesis, because zebrafish has been used as a model to human diseases, due to its handling easiness, the optical clarity of its embryos, and the availability of physiological and structural methodologies. Furthermore, muscle is an important target of the drug. We used several simvastatin concentrations at different zebrafish developmental stages and studied survival rate, morphology, and physiology of the embryos. Our results show that high levels of simvastatin induce structural damage whereas low doses induce minor structural changes, impaired movements, and reduced heart beating. Morphological alterations include changes in embryo and somite size and septa shape. Physiological changes include movement reduction and slower heartbeat. These effects could be reversed by the addition of exogenous cholesterol. Moreover, we quantified the total cell number during zebrafish development and demonstrated a large reduction in cell number after statin treatment. Since we could classify the alterations induced by simvastatin in three distinct phenotypes, we speculate that simvastatin acts through more than one mechanism and could affect both cell replication and/or cell death and muscle function. Our data can contribute to the understanding of the molecular and cellular basis of the mechanisms of action of simvastatin.

  13. Alterations in zebrafish development induced by simvastatin: Comprehensive morphological and physiological study, focusing on muscle

    PubMed Central

    Campos, Laise M; Rios, Eduardo A; Guapyassu, Livia; Midlej, Victor; Atella, Georgia C; Herculano-Houzel, Suzana; Benchimol, Marlene; Mermelstein, Claudia

    2016-01-01

    The cholesterol synthesis inhibitor simvastatin, which is used to treat cardiovascular diseases, has severe collateral effects. We decided to comprehensively study the effects of simvastatin in zebrafish development and in myogenesis, because zebrafish has been used as a model to human diseases, due to its handling easiness, the optical clarity of its embryos, and the availability of physiological and structural methodologies. Furthermore, muscle is an important target of the drug. We used several simvastatin concentrations at different zebrafish developmental stages and studied survival rate, morphology, and physiology of the embryos. Our results show that high levels of simvastatin induce structural damage whereas low doses induce minor structural changes, impaired movements, and reduced heart beating. Morphological alterations include changes in embryo and somite size and septa shape. Physiological changes include movement reduction and slower heartbeat. These effects could be reversed by the addition of exogenous cholesterol. Moreover, we quantified the total cell number during zebrafish development and demonstrated a large reduction in cell number after statin treatment. Since we could classify the alterations induced by simvastatin in three distinct phenotypes, we speculate that simvastatin acts through more than one mechanism and could affect both cell replication and/or cell death and muscle function. Our data can contribute to the understanding of the molecular and cellular basis of the mechanisms of action of simvastatin. PMID:27444151

  14. Co-ingestion of carbohydrate and whey protein increases fasted rates of muscle protein synthesis immediately after resistance exercise in rats

    PubMed Central

    Wang, Wanyi; Ding, Zhenping; Solares, Geoffrey J.; Choi, Soon-Mi; Wang, Bo; Yoon, Aram; Farrar, Roger P.; Ivy, John L.

    2017-01-01

    The objective of the study was to investigate whether co-ingestion of carbohydrate and protein as compared with protein alone augments muscle protein synthesis (MPS) during early exercise recovery. Two months old rats performed 10 repetitions of ladder climbing with 75% of body weight attached to their tails. Placebo (PLA), whey protein (WP), or whey protein plus carbohydrate (CP) was then given to rats by gavage. An additional group of sedentary rats (SED) was used as controls. Blood samples were collected immediately and at either 1 or 2 h after exercise. The flexor hallucis longus muscle was excised at 1 or 2 h post exercise for analysis of MPS and related signaling proteins. MPS was significantly increased by CP compared with PLA (p<0.05), and approached significance compared with WP at 1 h post exercise (p = 0.08). CP yielded a greater phosphorylation of mTOR compared with SED and PLA at 1 h post exercise and SED and WP at 2 h post exercise. CP also increased phosphorylation of p70S6K compared with SED at 1 and 2 h post exercise. 4E-BP1 phosphorylation was inhibited by PLA at 1 h but elevated by WP and CP at 2 h post exercise relative to SED. The phosphorylation of AMPK was elevated by exercise at 1 h post exercise, and this elevated level was sustained only in the WP group at 2 h. The phosphorylation of Akt, GSK3, and eIF2Bε were unchanged by treatments. Plasma insulin was transiently increased by CP at 1 h post exercise. In conclusion, post-exercise CP supplementation increases MPS post exercise relative to PLA and possibly WP, which may have been mediated by greater activation of the mTOR signaling pathway. PMID:28296942

  15. Co-ingestion of carbohydrate and whey protein increases fasted rates of muscle protein synthesis immediately after resistance exercise in rats.

    PubMed

    Wang, Wanyi; Ding, Zhenping; Solares, Geoffrey J; Choi, Soon-Mi; Wang, Bo; Yoon, Aram; Farrar, Roger P; Ivy, John L

    2017-01-01

    The objective of the study was to investigate whether co-ingestion of carbohydrate and protein as compared with protein alone augments muscle protein synthesis (MPS) during early exercise recovery. Two months old rats performed 10 repetitions of ladder climbing with 75% of body weight attached to their tails. Placebo (PLA), whey protein (WP), or whey protein plus carbohydrate (CP) was then given to rats by gavage. An additional group of sedentary rats (SED) was used as controls. Blood samples were collected immediately and at either 1 or 2 h after exercise. The flexor hallucis longus muscle was excised at 1 or 2 h post exercise for analysis of MPS and related signaling proteins. MPS was significantly increased by CP compared with PLA (p<0.05), and approached significance compared with WP at 1 h post exercise (p = 0.08). CP yielded a greater phosphorylation of mTOR compared with SED and PLA at 1 h post exercise and SED and WP at 2 h post exercise. CP also increased phosphorylation of p70S6K compared with SED at 1 and 2 h post exercise. 4E-BP1 phosphorylation was inhibited by PLA at 1 h but elevated by WP and CP at 2 h post exercise relative to SED. The phosphorylation of AMPK was elevated by exercise at 1 h post exercise, and this elevated level was sustained only in the WP group at 2 h. The phosphorylation of Akt, GSK3, and eIF2Bε were unchanged by treatments. Plasma insulin was transiently increased by CP at 1 h post exercise. In conclusion, post-exercise CP supplementation increases MPS post exercise relative to PLA and possibly WP, which may have been mediated by greater activation of the mTOR signaling pathway.

  16. Altered turnover of calcium regulatory proteins of the sarcoplasmic reticulum in aged skeletal muscle.

    PubMed

    Ferrington, D A; Krainev, A G; Bigelow, D J

    1998-03-06

    We have measured the in vivo protein turnover for the major calcium regulatory proteins of the sarcoplasmic reticulum from the skeletal muscle of young adult (7 months) and aged (28 months) Fischer 344 rats. From the time course of the incorporation and decay of protein-associated radioactivity after a pulse injection of [14C]leucine and correcting for leucine reutilization, in young rats, the apparent half-lives for calsequestrin, the 53-kDa glycoprotein, and ryanodine receptor are 5.4 +/- 0.4, 6.3 +/- 1.3, and 8.3 +/- 1.3 days, respectively. A half-life of 14.5 +/- 2.5 days was estimated for the Ca-ATPase isolated from young muscle. Differences in protein turnover associated with aging were determined using sequential injection of two different isotopic labels ([14C]leucine and [3H]leucine) to provide an estimate of protein synthesis and degradation within the same animal. The Ca-ATPase and ryanodine receptor isolated from aged muscle exhibits 27 +/- 5% and 25 +/- 3% slower protein turnover, respectively, relative to that from young muscle. In contrast, the 53-kDa glycoprotein exhibits a 25 +/- 5% more rapid turnover in aged SR, while calsequestrin exhibits no age-dependent alteration in turnover. Statistical analysis comparing the sensitivity of various methods for discriminating different rates of protein turnover validates the approach used in this study and demonstrates that the use of two isotopic labels provides at least a 6-fold more sensitive means to detect age-related differences in protein turnover relative to other methods.

  17. Altered activation of the antagonist muscle during practice compromises motor learning in older adults.

    PubMed

    Chen, Yen-Ting; Kwon, MinHyuk; Fox, Emily J; Christou, Evangelos A

    2014-08-15

    Aging impairs the activation of muscle; however, it remains unclear whether it contributes to deficits in motor learning in older adults. The purpose of this study was to determine whether altered activation of antagonistic muscles in older adults during practice inhibits their ability to transfer a motor task ipsilaterally. Twenty young (25.1 ± 3.9 yr; 10 men, 10 women) and twenty older adults (71.5 ± 4.8 yr; 10 men, 10 women) participated. Half of the subjects practiced 100 trials of a rapid goal-directed task with ankle dorsiflexion and were tested 1 day later with elbow flexion (transfer). The rest did not perform any ankle practice and only performed the task with elbow flexion. The goal-directed task consisted of rapid movement (180 ms) to match a spatiotemporal target. For each limb, we recorded the EMG burst activity of the primary agonist and antagonist muscles. The rate of improvement during task acquisition (practice) was similar for young and older adults (P > 0.3). In contrast, only young adults were able to transfer the task to the upper limb. Specifically, young adults who practiced ankle dorsiflexion exhibited ∼30% (P < 0.05) lower movement error and ∼60% (P < 0.05) lower antagonist EMG burst activity compared with older adults who received equal practice and young adults who did not receive any ankle dorsiflexion practice. These results provide novel evidence that the deficient motor learning in older adults may be related to a differential activation of the antagonist muscle, which compromises their ability to acquire the task during practice. Copyright © 2014 the American Physiological Society.

  18. Altered activation of the antagonist muscle during practice compromises motor learning in older adults

    PubMed Central

    Chen, Yen-Ting; Kwon, MinHyuk; Fox, Emily J.

    2014-01-01

    Aging impairs the activation of muscle; however, it remains unclear whether it contributes to deficits in motor learning in older adults. The purpose of this study was to determine whether altered activation of antagonistic muscles in older adults during practice inhibits their ability to transfer a motor task ipsilaterally. Twenty young (25.1 ± 3.9 yr; 10 men, 10 women) and twenty older adults (71.5 ± 4.8 yr; 10 men, 10 women) participated. Half of the subjects practiced 100 trials of a rapid goal-directed task with ankle dorsiflexion and were tested 1 day later with elbow flexion (transfer). The rest did not perform any ankle practice and only performed the task with elbow flexion. The goal-directed task consisted of rapid movement (180 ms) to match a spatiotemporal target. For each limb, we recorded the EMG burst activity of the primary agonist and antagonist muscles. The rate of improvement during task acquisition (practice) was similar for young and older adults (P > 0.3). In contrast, only young adults were able to transfer the task to the upper limb. Specifically, young adults who practiced ankle dorsiflexion exhibited ∼30% (P < 0.05) lower movement error and ∼60% (P < 0.05) lower antagonist EMG burst activity compared with older adults who received equal practice and young adults who did not receive any ankle dorsiflexion practice. These results provide novel evidence that the deficient motor learning in older adults may be related to a differential activation of the antagonist muscle, which compromises their ability to acquire the task during practice. PMID:24848478

  19. Reducing dietary fat from a meal increases the bioavailability of exogenous carbohydrate without altering plasma glucose concentration

    PubMed Central

    Knuth, Nicolas D.; Shrivastava, Cara R.; Horowitz, Jeffrey F.

    2009-01-01

    The primary goal of this study was to determine the acute glycemic and endocrine responses to the reduction of fat content from a meal. On three separate occasions, nine overweight subjects (body mass index = 30 ± 1 kg/m2; 5 men, 4 women) consumed 1) a control meal (∼800 kcal; 100 g of carbohydrate, 31 g of fat, and 30 g of protein), 2) a low-fat meal (∼530 kcal; 100 g of carbohydrate, 1 g of fat, and 30 g of protein), or 3) a low-fat meal plus lipid infusion [same meal as low-fat meal, but the total energy provided was the same as control (800 kcal), with the “missing” fat (∼30 g) provided via an intravenous lipid infusion]. All three meals contained [13C]glucose (3 mg/kg body wt) to assess the bioavailability of ingested glucose. During the 5-h period after each meal, we measured the recovery of [13C]glucose in plasma, plasma glucose, and insulin concentrations. We also measured plasma concentration of the gastrointestinal peptides: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and peptide YY3-36 (PYY3-36). The recovery of the ingested [13C]glucose in the hour after ingestion was greater (P < 0.05) after the low-fat than after the control meal [area under the curve (AUC): 1,206 ± 252 and 687 ± 161 μM·h, respectively]. However, removing dietary fat from the meal did not affect the plasma concentration of glucose or insulin. Importantly, [13C]glucose recovery was not different during the low-fat and lipid infusion trials (AUC: 1,206 ± 252 and 1,134 ± 247 μM·h, respectively), indicating that the accelerated delivery of exogenous glucose found after removing fat from the meal is due exclusively to the reduction of fat in the gastrointestinal tract. In parallel with these findings, the reduction in fat calories from the meal reduced plasma concentration of GIP, GLP-1, and PYY3-36. In summary, these data suggest that removing fat from the diet expedited exogenous glucose delivery into the systemic circulation

  20. Maternal bisphenol A exposure alters rat offspring hepatic and skeletal muscle insulin signaling protein abundance.

    PubMed

    Galyon, Kristina D; Farshidi, Farnoosh; Han, Guang; Ross, Michael G; Desai, Mina; Jellyman, Juanita K

    2017-03-01

    skeletal muscle. In adult female bisphenol A offspring, the skeletal muscle protein abundance of glucose transporter 4 was 0.4-fold of the control. Maternal bisphenol A had sex- and tissue-specific effects on insulin signaling components, which may contribute to increased risk of glucose intolerance in offspring. Glucose transporters were consistently altered at both ages as well as in both sexes and may contribute to glucose intolerance. These data suggest that maternal bisphenol A exposure should be limited during pregnancy and lactation. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Postnatal exposure to a high-carbohydrate diet interferes epigenetically with thyroid hormone receptor induction of the adult male rat skeletal muscle glucose transporter isoform 4 expression.

    PubMed

    Raychaudhuri, Nupur; Thamotharan, Shanthie; Srinivasan, Malathi; Mahmood, Saleh; Patel, Mulchand S; Devaskar, Sherin U

    2014-10-01

    Early life nutritional intervention causes adult-onset insulin resistance and obesity in rats. Thyroid hormone receptor (TR), in turn, transcriptionally enhances skeletal muscle Glut4 expression. We tested the hypothesis that reduced circulating thyroid-stimulating hormone and T4 concentrations encountered in postnatal (PN4-PN24) high-carbohydrate (HC) milk formula-fed versus the mother-fed controls (MF) would epigenetically interfere with TR induction of adult (100 days) male rat skeletal muscle Glut4 expression, thereby providing a molecular mechanism mediating insulin resistance. We observed increased DNA methylation of the CpG island with enhanced recruitment of Dnmt3a, Dnmt3b and MeCP2 in the glut4 promoter region along with reduced acetylation of histone (H)2A.Z and H4 particularly at the H4.lysine (K)16 residue, which was predominantly mediated by histone deacetylase 4 (HDAC4). This was followed by enhanced recruitment of heterochromatin protein 1β to the glut4 promoter with increased Suv39H1 methylase concentrations. These changes reduced TR binding of the T3 response element of the glut4 gene (TREs; -473 to -450 bp) detected qualitatively in vivo (electromobility shift assay) and quantified ex vivo (chromatin immunoprecipitation). In addition, the recruitment of steroid receptor coactivator and CREB-binding protein to the glut4 promoter-protein complex was reduced. Co-immunoprecipitation experiments confirmed the interaction between TR and CBP to be reduced and HDAC4 to be enhanced in HC versus MF groups. These molecular changes were associated with diminished skeletal muscle Glut4 mRNA and protein concentrations. We conclude that early postnatal exposure to HC diet epigenetically reduced TR induction of adult male skeletal muscle Glut4 expression, uncovering novel molecular mechanisms contributing to adult insulin resistance and obesity.

  2. Increased net muscle protein balance in response to simultaneous and separate ingestion of carbohydrate and essential amino acids following resistance exercise.

    PubMed

    Witard, Oliver C; Cocke, Tara L; Ferrando, Arny A; Wolfe, Robert R; Tipton, Kevin D

    2014-03-01

    Relative to essential amino acids (EAAs), carbohydrate (CHO) ingestion stimulates a delayed response of net muscle protein balance (NBAL). We investigated if staggered ingestion of CHO and EAA would superimpose the response of NBAL following resistance exercise, thus resulting in maximal anabolic stimulation. Eight recreationally trained subjects completed 2 trials: combined (COMB - drink 1, CHO+EAA; drink 2, placebo) and separated (SEP - drink 1, CHO; drink 2, EAA) post-exercise ingestion of CHO and EAA. Drink 1 was administered 1 h following an acute exercise bout and was followed 1 h later by drink 2. A primed, continuous infusion of l-[ring-(13)C6]-phenylalanine was combined with femoral arteriovenous sampling and muscle biopsies for the determination of muscle protein kinetics. Arterial amino acid concentrations increased following ingestion of EAA in both conditions. No difference between conditions was observed for phenylalanine delivery to the leg (COMB: 167 ± 23 μmol·min(-1)·(100 mL leg vol)(-1) × 6 h; SEP: 167 ± 21 μmol·min(-1)·(100 mL leg vol)(-1) × 6 h, P > 0.05). In the first hour following ingestion of the drink containing EAA, phenylalanine uptake was 50% greater for the SEP trial than the COMB trial. However, phenylalanine uptake was similar for COMB (110 ± 19 mg) and SEP (117 ± 24 mg) over the 6 h period. These data suggest that whereas separation of CHO and EAA ingestion following exercise may have a transient physiological impact on NBAL, this response is not reflected over a longer period. Thus, separation of CHO and EAA ingestion is unnecessary to optimize post-exercise muscle protein metabolism.

  3. Cause of exercise associated muscle cramps (EAMC)--altered neuromuscular control, dehydration or electrolyte depletion?

    PubMed

    Schwellnus, M P

    2009-06-01

    Exercise Associated Muscle Cramps (EAMC) is one of the most common conditions that require medical attention during or immediately after sports events. Despite the high prevalence of this condition the aetiology of EAMC in athletes is still not well understood. The purpose of this review is to examine current scientific evidence in support of (1) the "electrolyte depletion" and "dehydration" hypotheses and (2) the "altered neuromuscular control" hypothesis in the aetiology of EAMC. In this review, scientific evidence will, as far as possible, be presented using evidence-based medicine criteria. This is particularly relevant in this field, as the quality of experimental methodology varies considerably among studies that are commonly cited in support of hypotheses to explain the aetiology of EAMC. Scientific evidence in support of the "electrolyte depletion" and "dehydration" hypotheses for the aetiology of EAMC comes mainly from anecdotal clinical observations, case series totalling 18 cases, and one small (n = 10) case-control study. Results from four prospective cohort studies do not support these hypotheses. In addition, the "electrolyte depletion" and "dehydration" hypotheses do not offer plausible pathophysiological mechanisms with supporting scientific evidence that could adequately explain the clinical presentation and management of EAMC. Scientific evidence for the "altered neuromuscular control" hypothesis is based on evidence from research studies in human models of muscle cramping, epidemiological studies in cramping athletes, and animal experimental data. Whilst it is clear that further evidence to support the "altered neuromuscular control" hypothesis is also required, research data are accumulating that support this as the principal pathophysiological mechanism for the aetiology of EAMC.

  4. Deregulation of the Protocadherin Gene FAT1 Alters Muscle Shapes: Implications for the Pathogenesis of Facioscapulohumeral Dystrophy

    PubMed Central

    Caruso, Nathalie; Herberth, Balàzs; Bartoli, Marc; Puppo, Francesca; Dumonceaux, Julie; Zimmermann, Angela; Denadai, Simon; Lebossé, Marie; Roche, Stephane; Geng, Linda; Magdinier, Frederique; Attarian, Shahram; Bernard, Rafaelle; Maina, Flavio; Levy, Nicolas; Helmbacher, Françoise

    2013-01-01

    Generation of skeletal muscles with forms adapted to their function is essential for normal movement. Muscle shape is patterned by the coordinated polarity of collectively migrating myoblasts. Constitutive inactivation of the protocadherin gene Fat1 uncoupled individual myoblast polarity within chains, altering the shape of selective groups of muscles in the shoulder and face. These shape abnormalities were followed by early onset regionalised muscle defects in adult Fat1-deficient mice. Tissue-specific ablation of Fat1 driven by Pax3-cre reproduced muscle shape defects in limb but not face muscles, indicating a cell-autonomous contribution of Fat1 in migrating muscle precursors. Strikingly, the topography of muscle abnormalities caused by Fat1 loss-of-function resembles that of human patients with facioscapulohumeral dystrophy (FSHD). FAT1 lies near the critical locus involved in causing FSHD, and Fat1 mutant mice also show retinal vasculopathy, mimicking another symptom of FSHD, and showed abnormal inner ear patterning, predictive of deafness, reminiscent of another burden of FSHD. Muscle-specific reduction of FAT1 expression and promoter silencing was observed in foetal FSHD1 cases. CGH array-based studies identified deletion polymorphisms within a putative regulatory enhancer of FAT1, predictive of tissue-specific depletion of FAT1 expression, which preferentially segregate with FSHD. Our study identifies FAT1 as a critical determinant of muscle form, misregulation of which associates with FSHD. PMID:23785297

  5. Ablation of GalNAc-4-sulfotransferase-1 enhances reproduction by altering the carbohydrate structures of luteinizing hormone in mice

    PubMed Central

    Mi, Yiling; Fiete, Dorothy; Baenziger, Jacques U.

    2008-01-01

    Luteinizing hormone (LH), produced in the anterior lobe of the pituitary, is a member of the hypothalamic-pituitary-gonad axis that is required for production of the sex hormones estradiol, progesterone, and testosterone. Perturbations in levels of hormones associated with this axis can result in defects in sexual development and maturity. LH bears unique N-linked carbohydrate units that terminate with a sulfated N-acetylgalactosamine structure (GalNAc-4-SO4) that mediates its clearance from the blood. To determine the significance of this terminal structure, we ablated the gene encoding the sulfotransferase responsible for sulfate addition to GalNAc on LH, GalNAc-4-sulfotransferase-1 (GalNAc-4-ST1) in mice. Mice lacking GalNAc-4-ST1 exhibited increased levels of circulating LH. In male mice, this resulted in elevated levels of testosterone and precocious maturation of testis and seminal vesicles. Female mice lacking GalNAc-4-ST1 demonstrated elevated estrogen levels and exhibited precocious sexual maturation and increased fecundity. Female mice remained in estrus for prolonged periods and produced almost 50% more litters per mouse than wild-type mice over the same period of time. Thus, sulfate modification of the terminal glycosylation of LH plays a central role in regulating the hypothalamic-pituitary-gonad axis in vivo. PMID:18431515

  6. Exogenously applied 24-epi brassinolide reduces lignification and alters cell wall carbohydrate biosynthesis in the secondary xylem of Liriodendron tulipifera.

    PubMed

    Jin, Hyunjung; Do, Jihye; Shin, Soo-Jeong; Choi, Joon Weon; Choi, Young Im; Kim, Wook; Kwon, Mi

    2014-05-01

    The roles of brassinosteroids (BRs) in vasculature development have been implicated based on an analysis of Arabidopsis BR mutants and suspension cells of Zinnia elegans. However, the effects of BRs in vascular development of a woody species have not been demonstrated. In this study, 24-epi brassinolide (BL) was applied to the vascular cambium of a vertical stem of a 2-year-old Liriodendron, and the resulting chemical and anatomical phenotypes were characterized to uncover the roles of BRs in secondary xylem formation of a woody species. The growth in xylary cells was clearly promoted when treated with BL. Statistical analysis indicated that the length of both types of xylary cells (fiber and vessel elements) increased significantly after BL application. Histochemical analysis demonstrated that BL-induced growth promotion involved the acceleration of cell division and cell elongation. Histochemical and expression analysis of several lignin biosynthetic genes indicated that most genes in the phenylpropanoid pathway were significantly down-regulated in BL-treated stems compared to that in control stems. Chemical analysis of secondary xylem demonstrated that BL treatment induced significant modification in the cell wall carbohydrates, including biosynthesis of hemicellulose and cellulose. Lignocellulose crystallinity decreased significantly, and the hemicellulose composition changed with significant increases in galactan and arabinan. Thus, BL has regulatory roles in the biosynthesis and modification of secondary cell wall components and cell wall assembly during secondary xylem development in woody plants.

  7. Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.

    PubMed

    Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J

    2016-10-14

    GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2(fl/fl)) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2(fl/fl) mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2(fl/fl) mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Carbohydrates for training and competition.

    PubMed

    Burke, Louise M; Hawley, John A; Wong, Stephen H S; Jeukendrup, Asker E

    2011-01-01

    An athlete's carbohydrate intake can be judged by whether total daily intake and the timing of consumption in relation to exercise maintain adequate carbohydrate substrate for the muscle and central nervous system ("high carbohydrate availability") or whether carbohydrate fuel sources are limiting for the daily exercise programme ("low carbohydrate availability"). Carbohydrate availability is increased by consuming carbohydrate in the hours or days prior to the session, intake during exercise, and refuelling during recovery between sessions. This is important for the competition setting or for high-intensity training where optimal performance is desired. Carbohydrate intake during exercise should be scaled according to the characteristics of the event. During sustained high-intensity sports lasting ~1 h, small amounts of carbohydrate, including even mouth-rinsing, enhance performance via central nervous system effects. While 30-60 g · h(-1) is an appropriate target for sports of longer duration, events >2.5 h may benefit from higher intakes of up to 90 g · h(-1). Products containing special blends of different carbohydrates may maximize absorption of carbohydrate at such high rates. In real life, athletes undertake training sessions with varying carbohydrate availability. Whether implementing additional "train-low" strategies to increase the training adaptation leads to enhanced performance in well-trained individuals is unclear.

  9. Altered Expression of Human Smooth Muscle Myosin Phosphatase Targeting (MYPT) Isovariants with Pregnancy and Labor.

    PubMed

    Lartey, Jon; Taggart, Julie; Robson, Stephen; Taggart, Michael

    2016-01-01

    Myosin light-chain phosphatase is a trimeric protein that hydrolyses phosphorylated myosin II light chains (MYLII) to cause relaxation in smooth muscle cells including those of the uterus. A major component of the phosphatase is the myosin targeting subunit (MYPT), which directs a catalytic subunit to dephosphorylate MYLII. There are 5 main MYPT family members (MYPT1 (PPP1R12A), MYPT2 (PPP1R12B), MYPT3 (PPP1R16A), myosin binding subunit 85 MBS85 (PPP1R12C) and TIMAP (TGF-beta-inhibited membrane-associated protein (PPP1R16B)). Nitric oxide (NO)-mediated smooth muscle relaxation has in part been attributed to activation of the phosphatase by PKG binding to a leucine zipper (LZ) dimerization domain located at the carboxyl-terminus of PPP1R12A. In animal studies, alternative splicing of PPP1R12A can lead to the inclusion of a 31-nucleotide exonic segment that generates a LZ negative (LZ-) isovariant rendering the phosphatase less sensitive to NO vasodilators and alterations in PPP1R12ALZ- and LZ+ expression have been linked to phenotypic changes in smooth muscle function. Moreover, PPP1R12B and PPP1R12C, but not PPP1R16A or PPP1R16B, have the potential for LZ+/LZ- alternative splicing. Yet, by comparison to animal studies, the information on human MYPT genomic sequences/mRNA expressions is scant. As uterine smooth muscle undergoes substantial remodeling during pregnancy we were interested in establishing the patterns of expression of human MYPT isovariants during this process and also following labor onset as this could have important implications for determining successful pregnancy outcome. We used cross-species genome alignment, to infer putative human sequences not available in the public domain, and isovariant-specific quantitative PCR, to analyse the expression of mRNA encoding putative LZ+ and LZ- forms of PPP1R12A, PPP1R12B and PPP1R12C as well as canonical PPP1R16A and PPP1R16B genes in human uterine smooth muscle from non-pregnant, pregnant and in

  10. Altered Expression of Human Smooth Muscle Myosin Phosphatase Targeting (MYPT) Isovariants with Pregnancy and Labor

    PubMed Central

    Taggart, Julie; Robson, Stephen; Taggart, Michael

    2016-01-01

    Background Myosin light-chain phosphatase is a trimeric protein that hydrolyses phosphorylated myosin II light chains (MYLII) to cause relaxation in smooth muscle cells including those of the uterus. A major component of the phosphatase is the myosin targeting subunit (MYPT), which directs a catalytic subunit to dephosphorylate MYLII. There are 5 main MYPT family members (MYPT1 (PPP1R12A), MYPT2 (PPP1R12B), MYPT3 (PPP1R16A), myosin binding subunit 85 MBS85 (PPP1R12C) and TIMAP (TGF-beta-inhibited membrane-associated protein (PPP1R16B)). Nitric oxide (NO)-mediated smooth muscle relaxation has in part been attributed to activation of the phosphatase by PKG binding to a leucine zipper (LZ) dimerization domain located at the carboxyl-terminus of PPP1R12A. In animal studies, alternative splicing of PPP1R12A can lead to the inclusion of a 31-nucleotide exonic segment that generates a LZ negative (LZ-) isovariant rendering the phosphatase less sensitive to NO vasodilators and alterations in PPP1R12ALZ- and LZ+ expression have been linked to phenotypic changes in smooth muscle function. Moreover, PPP1R12B and PPP1R12C, but not PPP1R16A or PPP1R16B, have the potential for LZ+/LZ- alternative splicing. Yet, by comparison to animal studies, the information on human MYPT genomic sequences/mRNA expressions is scant. As uterine smooth muscle undergoes substantial remodeling during pregnancy we were interested in establishing the patterns of expression of human MYPT isovariants during this process and also following labor onset as this could have important implications for determining successful pregnancy outcome. Objectives We used cross-species genome alignment, to infer putative human sequences not available in the public domain, and isovariant-specific quantitative PCR, to analyse the expression of mRNA encoding putative LZ+ and LZ- forms of PPP1R12A, PPP1R12B and PPP1R12C as well as canonical PPP1R16A and PPP1R16B genes in human uterine smooth muscle from non

  11. Niacin in pharmacological doses alters microRNA expression in skeletal muscle of obese Zucker rats.

    PubMed

    Couturier, Aline; Keller, Janine; Most, Erika; Ringseis, Robert; Eder, Klaus

    2014-01-01

    Administration of pharmacological niacin doses was recently reported to have pronounced effects on skeletal muscle gene expression and phenotype in obese Zucker rats, with the molecular mechanisms underlying the alteration of gene expression being completely unknown. Since miRNAs have been shown to play a critical role for gene expression through inducing miRNA-mRNA interactions which results in the degradation of specific mRNAs or the repression of protein translation, we herein aimed to investigate the influence of niacin at pharmacological doses on the miRNA expression profile in skeletal muscle of obese Zucker rats fed either a control diet with 30 mg supplemented niacin/kg diet or a high-niacin diet with 780 mg supplemented niacin/kg diet for 4 wk. miRNA microarray analysis revealed that 42 out of a total of 259 miRNAs were differentially expressed (adjusted P-value <0.05), 20 being down-regulated and 22 being up-regulated, between the niacin group and the control group. Using a biostatistics approach, we could demonstrate that the most strongly up-regulated (log2 ratio ≥0.5) and down-regulated (log2 ratio ≤-0.5) miRNAs target approximately 1,800 mRNAs. Gene-term enrichment analysis showed that many of the predicted target mRNAs from the most strongly regulated miRNAs were involved in molecular processes dealing with gene transcription such as DNA binding, transcription regulator activity, transcription factor binding and in important regulatory pathways such as Wnt signaling and MAPK signaling. In conclusion, the present study shows for the first time that pharmacological niacin doses alter the expression of miRNAs in skeletal muscle of obese Zucker rats and that the niacin-regulated miRNAs target a large set of genes and pathways which are involved in gene regulatory activity indicating that at least some of the recently reported effects of niacin on skeletal muscle gene expression and phenotype in obese Zucker rats are mediated through mi

  12. Niacin in Pharmacological Doses Alters MicroRNA Expression in Skeletal Muscle of Obese Zucker Rats

    PubMed Central

    Most, Erika; Ringseis, Robert; Eder, Klaus

    2014-01-01

    Administration of pharmacological niacin doses was recently reported to have pronounced effects on skeletal muscle gene expression and phenotype in obese Zucker rats, with the molecular mechanisms underlying the alteration of gene expression being completely unknown. Since miRNAs have been shown to play a critical role for gene expression through inducing miRNA-mRNA interactions which results in the degradation of specific mRNAs or the repression of protein translation, we herein aimed to investigate the influence of niacin at pharmacological doses on the miRNA expression profile in skeletal muscle of obese Zucker rats fed either a control diet with 30 mg supplemented niacin/kg diet or a high-niacin diet with 780 mg supplemented niacin/kg diet for 4 wk. miRNA microarray analysis revealed that 42 out of a total of 259 miRNAs were differentially expressed (adjusted P-value <0.05), 20 being down-regulated and 22 being up-regulated, between the niacin group and the control group. Using a biostatistics approach, we could demonstrate that the most strongly up-regulated (log2 ratio ≥0.5) and down-regulated (log2 ratio ≤−0.5) miRNAs target approximately 1,800 mRNAs. Gene-term enrichment analysis showed that many of the predicted target mRNAs from the most strongly regulated miRNAs were involved in molecular processes dealing with gene transcription such as DNA binding, transcription regulator activity, transcription factor binding and in important regulatory pathways such as Wnt signaling and MAPK signaling. In conclusion, the present study shows for the first time that pharmacological niacin doses alter the expression of miRNAs in skeletal muscle of obese Zucker rats and that the niacin-regulated miRNAs target a large set of genes and pathways which are involved in gene regulatory activity indicating that at least some of the recently reported effects of niacin on skeletal muscle gene expression and phenotype in obese Zucker rats are mediated through mi

  13. Alterations in Skeletal Muscle Function with Microgravity, and the Protective Effects of High Resistance Isometric and Isotonic Exercise

    NASA Technical Reports Server (NTRS)

    Fitts, R. H.; Hurst, J. E.; Norenberg, K. M.; Widrick, J. J.; Riley, D. A.; Bain, J. L. W.; Trappe, S. W.; Trappe, T. A.; Costill, D. L.

    1999-01-01

    Exposure to microgravity or models designed to mimic the unloaded condition, such as bed rest in humans and hindlimb unloading (HU) in rats leads to skeletal muscle atrophy, a loss in peak force and power, and an increased susceptibility to fatigue. The posterior compartment muscles of the lower leg (calf muscle group) appear to be particularly susceptible. Following only 1 wk in space or HU, rat soleus muscle showed a 30 to 40% loss in wet weight. After 3 wk of HU, almost all of the atrophied soleus fibers showed a significant increase in maximal shortening velocity (V(sub 0)), while only 25 to 30 % actually transitioned to fast fibers. The increased V(sub 0), was protective in that it reduced the decline in peak power associated with the reduced peak force. When the soleus is stimulated in situ following HU or zero-g one observes an increased rate and extent of fatigue, and in the former the increased fatigue is associated with a more rapid depletion of muscle glycogen and lactate production. Our working hypothesis is that following HU or spaceflight in rats and bed rest or spaceflight in humans limb skeletal muscles during contractile activity depend more on carbohydrates and less on fatty acids for their substrate supply. Baldwin et al. found 9 days of spaceflight to reduce by 37% the ability of both the high and low oxidative regions of the vastus muscle to oxidize long-chain fatty acids. This decline was not associated with any change in the enzymes of the tricarboxylic acid cycle or oxidation pathway. The purpose of the current research was to establish the extent of functional change in the slow type I and fast type H fibers of the human calf muscle following 17 days of spaceflight, and determine the cellular mechanisms of the observed changes. A second goal was to study the effectiveness of high resistance isotonic and isometric exercise in preventing the deleterious functional changes associated with unloading.

  14. Alterations in Skeletal Muscle Function with Microgravity, and the Protective Effects of High Resistance Isometric and Isotonic Exercise

    NASA Technical Reports Server (NTRS)

    Fitts, R. H.; Hurst, J. E.; Norenberg, K. M.; Widrick, J. J.; Riley, D. A.; Bain, J. L. W.; Trappe, S. W.; Trappe, T. A.; Costill, D. L.

    1999-01-01

    Exposure to microgravity or models designed to mimic the unloaded condition, such as bed rest in humans and hindlimb unloading (HU) in rats leads to skeletal muscle atrophy, a loss in peak force and power, and an increased susceptibility to fatigue. The posterior compartment muscles of the lower leg (calf muscle group) appear to be particularly susceptible. Following only 1 wk in space or HU, rat soleus muscle showed a 30 to 40% loss in wet weight. After 3 wk of HU, almost all of the atrophied soleus fibers showed a significant increase in maximal shortening velocity (V(sub 0)), while only 25 to 30 % actually transitioned to fast fibers. The increased V(sub 0), was protective in that it reduced the decline in peak power associated with the reduced peak force. When the soleus is stimulated in situ following HU or zero-g one observes an increased rate and extent of fatigue, and in the former the increased fatigue is associated with a more rapid depletion of muscle glycogen and lactate production. Our working hypothesis is that following HU or spaceflight in rats and bed rest or spaceflight in humans limb skeletal muscles during contractile activity depend more on carbohydrates and less on fatty acids for their substrate supply. Baldwin et al. found 9 days of spaceflight to reduce by 37% the ability of both the high and low oxidative regions of the vastus muscle to oxidize long-chain fatty acids. This decline was not associated with any change in the enzymes of the tricarboxylic acid cycle or oxidation pathway. The purpose of the current research was to establish the extent of functional change in the slow type I and fast type H fibers of the human calf muscle following 17 days of spaceflight, and determine the cellular mechanisms of the observed changes. A second goal was to study the effectiveness of high resistance isotonic and isometric exercise in preventing the deleterious functional changes associated with unloading.

  15. Inactivation of nitrate reductase alters metabolic branching of carbohydrate fermentation in the cyanobacterium Synechococcus sp. strain PCC 7002.

    PubMed

    Qian, Xiao; Kumaraswamy, G Kenchappa; Zhang, Shuyi; Gates, Colin; Ananyev, Gennady M; Bryant, Donald A; Dismukes, G Charles

    2016-05-01

    To produce cellular energy, cyanobacteria reduce nitrate as the preferred pathway over proton reduction (H2 evolution) by catabolizing glycogen under dark anaerobic conditions. This competition lowers H2 production by consuming a large fraction of the reducing equivalents (NADPH and NADH). To eliminate this competition, we constructed a knockout mutant of nitrate reductase, encoded by narB, in Synechococcus sp. PCC 7002. As expected, ΔnarB was able to take up intracellular nitrate but was unable to reduce it to nitrite or ammonia, and was unable to grow photoautotrophically on nitrate. During photoautotrophic growth on urea, ΔnarB significantly redirects biomass accumulation into glycogen at the expense of protein accumulation. During subsequent dark fermentation, metabolite concentrations--both the adenylate cellular energy charge (∼ATP) and the redox poise (NAD(P)H/NAD(P))--were independent of nitrate availability in ΔnarB, in contrast to the wild type (WT) control. The ΔnarB strain diverted more reducing equivalents from glycogen catabolism into reduced products, mainly H2 and d-lactate, by 6-fold (2.8% yield) and 2-fold (82.3% yield), respectively, than WT. Continuous removal of H2 from the fermentation medium (milking) further boosted net H2 production by 7-fold in ΔnarB, at the expense of less excreted lactate, resulting in a 49-fold combined increase in the net H2 evolution rate during 2 days of fermentation compared to the WT. The absence of nitrate reductase eliminated the inductive effect of nitrate addition on rerouting carbohydrate catabolism from glycolysis to the oxidative pentose phosphate (OPP) pathway, indicating that intracellular redox poise and not nitrate itself acts as the control switch for carbon flux branching between pathways.

  16. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome.

    PubMed

    Ong, Derrick K; Mitchell, Shaylyn B; Barrett, Jacqueline S; Shepherd, Sue J; Irving, Peter M; Biesiekierski, Jessica R; Smith, Stuart; Gibson, Peter R; Muir, Jane G

    2010-08-01

    Reduction of short-chain poorly absorbed carbohydrates (FODMAPs) in the diet reduces symptoms of irritable bowel syndrome (IBS). In the present study, we aimed to compare the patterns of breath hydrogen and methane and symptoms produced in response to diets that differed only in FODMAP content. Fifteen healthy subjects and 15 with IBS (Rome III criteria) undertook a single-blind, crossover intervention trial involving consuming provided diets that were either low (9 g/day) or high (50 g/day) in FODMAPs for 2 days. Food and gastrointestinal symptom diaries were kept and breath samples collected hourly over 14 h on day 2 of each diet. Higher levels of breath hydrogen were produced over the entire day with the high FODMAP diet for healthy volunteers (181 +/- 77 ppm.14 h vs 43 +/- 18; mean +/- SD P < 0.0001) and patients with IBS (242 +/- 79 vs 62 +/- 23; P < 0.0001), who had higher levels during each dietary period than the controls (P < 0.05). Breath methane, produced by 10 subjects within each group, was reduced with the high FODMAP intake in healthy subjects (47 +/- 29 vs 109 +/- 77; P = 0.043), but was not different in patients with IBS (126 +/- 153 vs 86 +/- 72). Gastrointestinal symptoms and lethargy were significantly induced by the high FODMAP diet in patients with IBS, while only increased flatus production was reported by healthy volunteers. Dietary FODMAPs induce prolonged hydrogen production in the intestine that is greater in IBS, influence the amount of methane produced, and induce gastrointestinal and systemic symptoms experienced by patients with IBS. The results offer mechanisms underlying the efficacy of the low FODMAP diet in IBS.

  17. Metal-supplemented diets alter carbohydrate levels in tissue and hemolymph of gypsy moth larvae (Lymantria dispar, Lymantriidae, Lepidoptera)

    SciTech Connect

    Ortel, J.

    1996-07-01

    Larvae of Lymantria dispar were exposed to two concentrations each of Cd, Pb, Cu, and Zn from hatching to day 3 of the fourth instar. The metals were applied via artificial diet (wheat germ diet); two control groups were reared on either an uncontaminated artificial diet (C) or on a natural diet (oak leaves, EF). High-pressure liquid chromatography (HPLC) was employed to analyze the hemolymph carbohydrates, whereas body glycogen and glucose were determined enzymatically. The results were analyzed with respect to diet-specific differences (oak leaves versus wheat germ diet) and metal exposure compared with the uncontaminated artificial diet. Hemolymph trehalose levels were higher in oak leaf-reared individuals than in those fed on the wheat germ diet (p < 0.01), whereas the opposite applied to the body glycogen and free glucose levels (p < 0.01). The average trehalose value of the control (C) (4.3 mg/ml) was reduced by metal contamination, dependent on both the metal itself and the concentration (Cd, Cu, Zn; 1.4--3.3 mg/ml). Sorbitol was not detected in the hemolymph of EF specimens, whereas it occurred in all artificial diet-fed groups. Metal- and dose-dependent differences in the hemolymph sorbitol levels were observed in the treatment groups, but not in the controls. Glycogen content increased in the low concentration of Cd, Pb, and Cu, whereas a decrease was observed for the low Cd and both Zn concentrations. Tissue free glucose was enhanced only in three of the metal groups. Generally, fresh and dry weights of larvae were reduced in all groups except the high Cu-contaminated one. The results may indicate that mass outbreaks of an important forest pest insect like L. dispar may be facilitated in metal-contaminated areas because parasitization success of antagonistic species may decline due to deterioration of nourishment within the metal-stressed host.

  18. Dietary leucine supplementation alters energy metabolism and induces slow-to-fast transitions in longissimus dorsi muscle of weanling piglets.

    PubMed

    Fan, Qiwen; Long, Baisheng; Yan, Guokai; Wang, Zhichang; Shi, Min; Bao, Xiaoyu; Hu, Jun; Li, Xiuzhi; Chen, Changqing; Zheng, Zilong; Yan, Xianghua

    2017-05-01

    Leucine plays an important role in promoting muscle protein synthesis and muscle remodelling. However, what percentage of leucine is appropriate in creep feed and what proteome profile alterations are caused by dietary leucine in the skeletal muscle of piglets remain elusive. In this case, we applied isobaric tags for relative and absolute quantitation to analyse the proteome profile of the longissimus dorsi muscles of weanling piglets fed a normal leucine diet (NL; 1·66 % leucine) and a high-leucine diet (HL; 2·1 % leucine). We identified 157 differentially expressed proteins between these two groups. Bioinformatics analysis of these proteins exhibited the suppression of oxidative phosphorylation and fatty acid β-oxidation, as well as the activation of glycolysis, in the HL group. For further confirmation, we identified that SDHB, ATP5F1, ACADM and HADHB were significantly down-regulated (P<0·01, except ATP5F1, P<0·05), whereas the glycolytic enzyme pyruvate kinase was significantly up-regulated (P<0·05) in the HL group. We also show that enhanced muscle protein synthesis and the transition from slow-to-fast fibres are altered by leucine. Together, these results indicate that leucine may alter energy metabolism and promote slow-to-fast transitions in the skeletal muscle of weanling piglets.

  19. Sodium chlorate, a major water disinfection byproduct, alters brush border membrane enzymes, carbohydrate metabolism and impairs antioxidant system of Wistar rat intestine.

    PubMed

    Ali, Shaikh Nisar; Ansari, Fariheen Aisha; Khan, Aijaz Ahmed; Mahmood, Riaz

    2017-05-01

    Sodium chlorate (NaClO3 ) is a widely used nonselective herbicide. It is also generated as a by-product during disinfection of drinking water by chlorine dioxide. The purpose of this study was to evaluate the effect of NaClO3 on rat intestine. Adult male rats were randomly divided into five groups: control and remaining four groups were administered orally different doses of NaClO3 and sacrificed 24 h after the treatment. The administration of NaClO3 produced acute oxidative stress in the intestine, which manifested in the form of markedly enhanced malondialdehyde levels and carbonyl content and lowered total sulfhydryl groups and glutathione levels. The activities of several brush border membrane (BBM) enzymes were greatly reduced as compared to control. There were alterations in the activities of various enzymes of carbohydrate metabolism and those involved in maintaining the antioxidant defense system. Histological studies support the biochemical results showing NaClO3 dose-dependent increase in tissue damage. Thus, the present study shows that oral administration of NaClO3 decreases the activities of BBM enzymes, induces oxidative stress, alters metabolic pathways, and impairs the antioxidant system of rat intestine. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1607-1616, 2017. © 2017 Wiley Periodicals, Inc.

  20. Uniconazole-induced starch accumulation in the bioenergy crop duckweed (Landoltia punctata) II: transcriptome alterations of pathways involved in carbohydrate metabolism and endogenous hormone crosstalk.

    PubMed

    Liu, Yang; Fang, Yang; Huang, Mengjun; Jin, Yanling; Sun, Jiaolong; Tao, Xiang; Zhang, Guohua; He, Kaize; Zhao, Yun; Zhao, Hai

    2015-01-01

    Landoltia punctata is a widely distributed duckweed species with great potential to accumulate enormous amounts of starch for bioethanol production. We found that L. punctata can accumulate starch rapidly accompanied by alterations in endogenous hormone levels after uniconazole application, but the relationship between endogenous hormones and starch accumulation is still unclear. After spraying fronds with 800 mg/L uniconazole, L. punctata can accumulate starch quickly, with a dry weight starch content of up to 48% after 240 h of growth compared to 15.7% in the control group. Electron microscopy showed that the starch granule content was elevated after uniconazole application. The activities of key enzymes involved in starch synthesis were also significantly increased. Moreover, the expression of regulatory elements of the cytokinin (CK), abscisic acid (ABA) and gibberellin (GA) signaling pathways that are involved in chlorophyll and starch metabolism also changed correspondingly. Importantly, the expression levels of key enzymes involved in starch biosynthesis were up-regulated, while transcript-encoding enzymes involved in starch degradation and other carbohydrate metabolic branches were down-regulated. The increase of endogenous ABA and CK levels positively promoted the activity of ADP-glucose pyrophosphorylase (AGPase) and chlorophyll content, while the decrease in endogenous GA levels inactivated α-amylase. Thus, the alterations of endogenous hormone levels resulted in starch accumulation due to regulation of the expression of genes involved in the starch metabolism pathway.

  1. Rotator cuff tendinopathy alters the muscle activity onset and kinematics of scapula.

    PubMed

    Leong, Hio Teng; Ng, Gabriel Yin-Fat; Chan, Shing Chung; Fu, Siu Ngor

    2017-08-01

    Athletes with rotator cuff (RC) tendinopathy demonstrate an aberrant pattern of scapular motion which might relate to deficits in the scapular muscles. This study aimed to determine whether alteration in scapular kinematics is associated with deficits in the activity onset of scapular muscles. Forty-three male volleyball players (17 asymptomatic and 26 with RC tendinopathy) joined the study. Three-dimensional scapular kinematics was quantified using an acromial marker cluster method. The activity onset of the upper (UT), middle (MT), and lower trapezius (LT), and serratus anterior (SA) during arm abduction was assessed with electromyography. Athletes with RC tendinopathy demonstrated less scapular upward rotation (6.6±2.3 vs. 8.2±1.1°, p=0.021) in the early phase of shoulder abduction from 0° to 30° when compared to asymptomatic athletes. The tendinopathy group had delayed activity onset of LT (14.1±31.4ms vs. 74.4±45.1ms, p<0.001) and SA (-44.9±26.0ms vs. 23.0±25.2ms, p<0.001) relative to UT when compared to the asymptomatic group. In asymptomatic athletes, earlier activity onset of MT and LT relative to UT was associated with more scapular upward rotation during 0-30° of abduction (r=0.665, p=0.021) and 30-60° of abduction (r=0.680, p=0.015), respectively. Our findings showed the control of the scapular upward rotation is related to the activity onset of the scapular muscles in athletes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. NO-mediated alterations in skeletal muscle nutritive blood flow and lactate metabolism in fibromyalgia.

    PubMed

    McIver, K L; Evans, C; Kraus, R M; Ispas, L; Sciotti, V M; Hickner, R C

    2006-01-01

    The purpose of these investigations was to determine if differences exist in skeletal muscle nutritive blood flow and lactate metabolism in women with fibromyalgia (FM) compared to healthy women (HC); furthermore, to determine if differences in nitric oxide-mediated systems account for any detected alterations in blood flow and lactate metabolism and contribute to exertional fatigue in FM. FM (n = 8) and HC (n = 8) underwent a cycle ergometry test of aerobic capacity, a muscle biopsy for determination of nitric oxide synthase (eNOS, nNOS, iNOS) content, and microdialysis for investigation of muscle nutritive blood flow and lactate metabolism. During prolonged (3h) resting conditions, the ethanol outflow/inflow ratio (inversely related to blood flow) increased in FM over time compared to HC (P < 0.05). FM also exhibited a reduced nutritive blood flow response to aerobic exercise (P < 0.05). There was an increase in dialysate lactate in response to acetylcholine in FM, and to sodium nitroprusside in both groups, with a greater rise in dialysate lactate in FM (P < 0.05). The iNOS protein content was higher in FM and was negatively correlated with total exercise time (r(2) = 0.462, P < 0.05). (1) There is reduced nutritive flow response to aerobic exercise and reduced maximal exercise time in FM that might relate to higher iNOS protein content and contribute to exertional fatigue in FM; (2) The increased dialysate lactate in FM in response to stimulation of NOS or a nitric oxide donor suggest that FM may be more sensitive than HC to the suppressive effect of nitric oxide on oxidative phosphorylation.

  3. Ageing and exercise training alter adrenergic vasomotor responses of rat skeletal muscle arterioles

    PubMed Central

    Donato, Anthony J; Lesniewski, Lisa A; Delp, Michael D

    2007-01-01

    Ageing is associated with increased leg vascular resistance and reductions in leg blood flow during rest and exercise, potentially predisposing older adults to a host of functional and cardiovascular complications. The purpose of these studies was to examine the effects and possible mechanisms of ageing and exercise training on arteriolar adrenergic vasoreactivity. Young and old male Fischer 344 rats were divided into young sedentary (YS), old sedentary (OS), young exercise-trained (YT) or old exercise-trained (OT) groups, where training consisted of chronic treadmill exercise. Isolated soleus (SOL) and gastrocnemius (GAS) muscle arterioles were studied in vitro. Responses to noradrenaline in endothelium-intact and endothelium-denuded arterioles, as well as during nitric oxide synthase (NOS) inhibition were determined. Vasodilator responses to isoproterenol and forskolin were also determined. Results: Noradrenaline-mediated vasoconstriction was increased in SOL arterioles with ageing, and exercise training in old rats attenuated α-adrenergic vasoconstriction in arterioles from both muscle types. Removal of the endothelium and NOS inhibition eliminated these ageing and training effects. Isoproterenol-mediated vasodilatation was impaired with ageing in SOL and GAS arterioles, and exercise training had little effect on this response. Forskolin-induced vasodilatation was not affected by age. The data demonstrate that ageing augments α-adrenergic vasoconstriction while exercise training attenuates this response, and both of these alterations are mediated through an endothelial α-receptor-NOS-signalling pathway. In contrast, ageing diminishes β-receptor-mediated vasodilatation, but this impairment is specific to the smooth muscle. These studies indicate that α- and β-adrenergic mechanisms may serve to increase systemic vascular resistance with ageing, and that the effects of exercise training on adrenergic vasomotor properties could contribute to the beneficial

  4. Aortic smooth muscle cell alterations in mice systemically exposed to arsenic.

    PubMed

    Chen, Shih-Chieh; Huang, Shin-Yin; Lin, Wen-Ting; Yang, Rei-Cheng; Yu, Hsin-Su

    2016-05-01

    Previous epidemiological studies showed that chronic arsenic exposure is related to increased cardiovascular disease incidence. The detailed biochemical mechanisms by which arsenic exerts its effects remain unknown. Vascular disease progression is characterized by smooth muscle cell (SMC) phenotypic switching, vessel wall reorganization, and platelet-derived growth factor (PDGF) production. The objective of this study was to examine early biochemical and structural changes in the aortas of ICR mice systemically exposed to arsenic. Animals were fed sodium arsenite (20 mg/kg) via gavage 5 days/week or Milli-Q water only (control) for 8 weeks. Aortic proteins were subjected to two-dimensional (2-D) differential gel electrophoresis and proteomic studies. Two 2-D gel protein spots were identified as the same protein, smooth muscle (SM)22α, using proteomics. SM22α and Rho kinase 2 gene and protein expression were significantly decreased in the aortic tissue of arsenic-exposed mice compared with that of control mice. No atherosclerotic lesion formation or tissue injury was detected in the aortic wall of either the arsenic-fed or the control group. However, the percent (%) SMC area of the aortic wall was significantly decreased in arsenic-fed mice compared with that in control mice. Additionally, the expression levels of PDGF-BB and early growth response-1 (Egr-1) were significantly higher in the arsenic group than that in the control group. These findings reveal biochemical alterations of SM22α, PDGF, and Egr-1 in conjunction with decreased SMC area in the aortic wall of arsenic-fed mice. Arsenic may initiate aortic SMC alterations that subsequently lead to vascular dysfunction.

  5. Musculoskeletal sensitization and sleep: chronic muscle pain fragments sleep of mice without altering its duration.

    PubMed

    Sutton, Blair C; Opp, Mark R

    2014-03-01

    Musculoskeletal pain in humans is often associated with poor sleep quality. We used a model in which mechanical hypersensitivity was induced by injection of acidified saline into muscle to study the impact of musculoskeletal sensitization on sleep of mice. A one month pre-clinical study was designed to determine the impact of musculoskeletal sensitization on sleep of C57BL/6J mice. We instrumented mice with telemeters to record the electroencephalogram (EEG) and body temperature. We used an established model of musculoskeletal sensitization in which mechanical hypersensitivity was induced using two unilateral injections of acidified saline (pH 4.0). The injections were given into the gastrocnemius muscle and spaced five days apart. EEG and body temperature recordings started prior to injections (baseline) and continued for three weeks after musculoskeletal sensitization was induced by the second injection. Mechanical hypersensitivity was assessed using von Frey filaments at baseline (before any injections) and on days 1, 3, 7, 14, and 21 after the second injection. Mice injected with acidified saline developed bilateral mechanical hypersensitivity at the hind paws as measured by von Frey testing and as compared to control mice and baseline data. Sleep during the light period was fragmented in experimental mice injected with acidified saline, and EEG spectra altered. Musculoskeletal sensitization did not alter the duration of time spent in wakefulness, non-rapid eye movement sleep, or rapid eye movement sleep. Musculoskeletal sensitization in this model results in a distinct sleep phenotype in which sleep is fragmented during the light period, but the overall duration of sleep is not changed. This study suggests the consequences of musculoskeletal pain include sleep disruption, an observation that has been made in the clinical literature but has yet to be studied using preclinical models.

  6. Primary motor cortex of the parkinsonian monkey: altered neuronal responses to muscle stretch

    PubMed Central

    Pasquereau, Benjamin; Turner, Robert S.

    2013-01-01

    Exaggeration of the long-latency stretch reflex (LLSR) is a characteristic neurophysiologic feature of Parkinson's disease (PD) that contributes to parkinsonian rigidity. To explore one frequently-hypothesized mechanism, we studied the effects of fast muscle stretches on neuronal activity in the macaque primary motor cortex (M1) before and after the induction of parkinsonism by unilateral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We compared results from the general population of M1 neurons and two antidromically-identified subpopulations: distant-projecting pyramidal-tract type neurons (PTNs) and intra-telecenphalic-type corticostriatal neurons (CSNs). Rapid rotations of elbow or wrist joints evoked short-latency responses in 62% of arm-related M1 neurons. As in PD, the late electromyographic responses that constitute the LLSR were enhanced following MPTP. This was accompanied by a shortening of M1 neuronal response latencies and a degradation of directional selectivity, but surprisingly, no increase in single unit response magnitudes. The results suggest that parkinsonism alters the timing and specificity of M1 responses to muscle stretch. Observation of an exaggerated LLSR with no change in the magnitude of proprioceptive responses in M1 is consistent with the idea that the increase in LLSR gain that contributes to parkinsonian rigidity is localized to the spinal cord. PMID:24324412

  7. Age-related alterations of skeletal muscle metabolism by intermittent hypoxia and TRH-analogue treatment.

    PubMed

    Pastoris, O; Dossena, M; Arnaboldi, R; Gorini, A; Villa, R F

    1994-01-01

    The characteristics of the energy metabolism were evaluated in the gastrocnemius muscle from 3- and 24-month-old rats in normoxia or subjected to either mild or severe chronic (4 weeks) intermittent normobaric hypoxia. Furthermore, 4-week treatment with saline or the TRH-analogue posatireline was performed. The muscular concentration of the following metabolites related to the energy metabolism was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate; energy charge potential. Furthermore the maximum rate of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The age-related decrease in muscular glucose 6-phosphate, pyruvate and alanine concentrations and increase in citrate concentration were consistent with the age-related decreased hexokinase and increased citrate synthase activities. Ageing was characterized by a decrease in muscular creatine phosphate concentration, while the energy mediators and the energy charge potential were unchanged. The chronic (4 weeks) intermittent normobaric mild and severe hypoxia-induced alterations of the components in the anaerobic glycolytic pathway, tricarboxylic acid cycle and energy storage, that were magnified in the skeletal muscle from the oldest animals. The effect of the chronic treatment with the TRH-analogue posatireline suggests that the action of central nervous system-acting drugs could also be related to their direct influence on the muscular biochemical mechanisms related to the energy transduction.

  8. Structural Analysis of Alterations in Zebrafish Muscle Differentiation Induced by Simvastatin and Their Recovery with Cholesterol

    PubMed Central

    Campos, Laise M.; Rios, Eduardo A.; Midlej, Victor; Atella, Georgia C.; Herculano-Houzel, Suzana; Benchimol, Marlene; Mermelstein, Claudia; Costa, Manoel Luís

    2015-01-01

    In vitro studies show that cholesterol is essential to myogenesis. We have been using zebrafish to overcome the limitations of the in vitro approach and to study the sub-cellular structures and processes involved during myogenesis. We use simvastatin—a drug widely used to prevent high levels of cholesterol and cardiovascular disease—during zebrafish skeletal muscle formation. Simvastatin is an efficient inhibitor of cholesterol synthesis that has various myotoxic consequences. Here, we employed simvastatin concentrations that cause either mild or severe morphological disturbances to observe changes in the cytoskeleton (intermediate filaments and microfilaments), extracellular matrix and adhesion markers by confocal microscopy. With low-dose simvastatin treatment, laminin was almost normal, and alpha-actinin was reduced in the myofibrils. With high simvastatin doses, laminin and vinculin were reduced and appeared discontinuous along the septa, with almost no myofibrils, and small amounts of desmin accumulating close to the septa. We also analyzed sub-cellular alterations in the embryos by electron microscopy, and demonstrate changes in embryo and somite size, septa shape, and in myofibril structure. These effects could be reversed by the addition of exogenous cholesterol. These results contribute to the understanding of the mechanisms of action of simvastatin in muscle cells in particular, and in the study of myogenesis in general. PMID:25786435

  9. Using broadband spatially resolved NIRS to assess muscle oxygenation during altered running protocols

    NASA Astrophysics Data System (ADS)

    Koukourakis, Georg; Vafiadou, Maria; Steimers, André; Geraskin, Dmitri; Neary, Patrick; Kohl-Bareis, Matthias

    2009-07-01

    We used spatially resolved near-infrared spectroscopy (SRS-NIRS) to assess calf and thigh muscle oxygenation during running on a motor-driven treadmill. Two protocols were used: An incremental speed protocol (velocity = 6 - 12 km/h, ▵v = 2 km/h) was performed in 3 minute stages, while a pacing paradigm modulated step frequency alternatively (2.3 Hz [SLow]; 3.3 Hz [SHigh]) during a constant velocity for 2 minutes each. A SRS-NIRS broadband system (600 - 1000 nm) was used to measure total haemoglobin concentration and oxygen saturation (SO2). An accelerometer was placed on the hip joints to measure limb acceleration through the experiment. The data showed that the calf (SO2 58 to 42%) desaturated to a significantly lower level than the thigh (61 to 54%). During the pacing protocol, SO2 was significantly different between the SLow vs. SHigh trials. Additionally, physiological data as measured by spirometry were different between the SLow vs. SHigh pacing trials (VO2 (2563+/- 586 vs. 2503 +/- 605 mL/min). Significant differences in VO2 at the same workload (speed) indicate alterations in mechanical efficiency. These data suggest that SRS broadband NIRS can be used to discern small changes in muscle oxygenation, making this device useful for metabolic exercise studies in addition to spirometry and movement monitoring by accelerometers.

  10. Loss of niche-satellite cell interactions in syndecan-3 null mice alters muscle progenitor cell homeostasis improving muscle regeneration.

    PubMed

    Pisconti, Addolorata; Banks, Glen B; Babaeijandaghi, Farshad; Betta, Nicole Dalla; Rossi, Fabio M V; Chamberlain, Jeffrey S; Olwin, Bradley B

    2016-01-01

    The skeletal muscle stem cell niche provides an environment that maintains quiescent satellite cells, required for skeletal muscle homeostasis and regeneration. Syndecan-3, a transmembrane proteoglycan expressed in satellite cells, supports communication with the niche, providing cell interactions and signals to maintain quiescent satellite cells. Syndecan-3 ablation unexpectedly improves regeneration in repeatedly injured muscle and in dystrophic mice, accompanied by the persistence of sublaminar and interstitial, proliferating myoblasts. Additionally, muscle aging is improved in syndecan-3 null mice. Since syndecan-3 null myofiber-associated satellite cells downregulate Pax7 and migrate away from the niche more readily than wild type cells, syxndecan-3 appears to regulate satellite cell homeostasis and satellite cell homing to the niche. Manipulating syndecan-3 provides a promising target for development of therapies to enhance muscle regeneration in muscular dystrophies and in aged muscle.

  11. Short-term alterations in carbohydrate energy intake in humans. Striking effects on hepatic glucose production, de novo lipogenesis, lipolysis, and whole-body fuel selection.

    PubMed Central

    Schwarz, J M; Neese, R A; Turner, S; Dare, D; Hellerstein, M K

    1995-01-01

    Short-term alterations in dietary carbohydrate (CHO) energy are known to alter whole-body fuel selection in humans, but the metabolic mechanisms remain unknown. We used stable isotope-mass spectrometric methods with indirect calorimetry in normal subjects to quantify the metabolic response to six dietary phases (5 d each), ranging from 50% surplus CHO (+50% CHO) to 50% deficient CHO (-50% CHO), and 50% surplus fat (+50% fat). Fasting hepatic glucose production (HGP) varied by > 40% from deficient to surplus CHO diets (1.78 +/- 0.08 vs 2.43 +/- 0.09 mg/kg per min, P < 0.01). Increased HGP on surplus CHO occurred despite significantly higher serum insulin concentrations. Lipolysis correlated inversely with CHO intake as did the proportion of whole-body lipolytic flux oxidized. Fractional de novo hepatic lipogenesis (DNL) increased more than 10-fold on surplus CHO and was unmeasurable on deficient CHO diets; thus, the preceding 5-d CHO intake could be inferred from DNL. Nevertheless, absolute hepatic DNL accounted for < 5g fatty acids synthesized per day even on +50% CHO. Whole-body CHO oxidation increased sixfold and fat oxidation decreased > 90% on surplus CHO diets. CHO oxidation was highly correlated with HGP (r2= 0.60). HGP could account for 85% of fasting CHO oxidation on +25% CHO and 67% on +50% CHO diets. Some oxidation of intracellular CHO stores was therefore also occurring. +50% fat diet had no effects on HGP, DNL, or fuel selection. We conclude that altered CHO intake alters HGP specifically and in a dose-dependent manner, that HGP may mediate the effects of CHO on whole-body fuel selection both by providing substrate and by altering serum insulin concentrations, that altered lipolysis and tissue oxidation efficiency contribute to changes in fat oxidation, and that surplus CHO is not substantially converted by the liver to fat as it spares fat oxidation, but that fractional DNL may nevertheless be a qualitative marker of recent CHO intake. Images PMID

  12. Adding protein to a carbohydrate supplement provided after endurance exercise enhances 4E-BP1 and RPS6 signaling in skeletal muscle.

    PubMed

    Morrison, Paul J; Hara, Daisuke; Ding, Zhenping; Ivy, John L

    2008-04-01

    To examine the role of both endurance exercise and nutrient supplementation on the activation of mRNA translation signaling pathways postexercise, rats were subjected to a 3-h swimming protocol. Immediately following exercise, the rats were provided with a solution containing either 23.7% wt/vol carbohydrates (CHO), 7.9% wt/vol protein (Pro), 31.6% wt/vol (23.7% wt/vol CHO + 7.9% wt/vol Pro) carbohydrates and Pro (CP), or a placebo (EX). The rats were then killed at 0, 30, and 90 min postexercise, and phosphorylation states of mammalian target of rapamycin (mTOR), ribosomal S6 kinase (p70(S6K)), ribosomal protein S6 (rpS6), and 4E-binding protein 1 (4E-BP1), were analyzed by immunoblot analysis in the red and white quadriceps muscle. Results demonstrated that rat groups provided with any of the three nutritional supplements (CHO, Pro, CP) transiently increased the phosphorylation states of mTOR, 4E-BP1, rpS6, and p70(S6K) compared with EX rats. Although CHO, Pro, and CP supplements phosphorylated mTOR and p70(S6K) after exercise, only CP elevated the phosphorylation of rpS6 above all other supplements 30 min postexercise and 4E-BP1 30 and 90 min postexercise. Furthermore, the phosphorylation states of 4E-BP1 (r(2) = 0.7942) and rpS6 (r(2) = 0.760) were highly correlated to insulin concentrations in each group. These results suggest that CP supplementation may be most effective in activating the mTOR-dependent signaling pathway in the postprandial state postexercise, and that there is a strong relationship between the insulin concentration and the activation of enzymes critical for mRNA translation.

  13. PGC1-α over-expression prevents metabolic alterations and soleus muscle atrophy in hindlimb unloaded mice.

    PubMed

    Cannavino, Jessica; Brocca, Lorenza; Sandri, Marco; Bottinelli, Roberto; Pellegrino, Maria Antonietta

    2014-10-15

    Prolonged skeletal muscle inactivity causes muscle fibre atrophy. Redox imbalance has been considered one of the major triggers of skeletal muscle disuse atrophy, but whether redox imbalance is actually the major cause or simply a consequence of muscle disuse remains of debate. Here we hypothesized that a metabolic stress mediated by PGC-1α down-regulation plays a major role in disuse atrophy. First we studied the adaptations of soleus to mice hindlimb unloading (HU) in the early phase of disuse (3 and 7 days of HU) with and without antioxidant treatment (trolox). HU caused a reduction in cross-sectional area, redox status alteration (NRF2, SOD1 and catalase up-regulation), and induction of the ubiquitin proteasome system (MuRF-1 and atrogin-1 mRNA up-regulation) and autophagy (Beclin1 and p62 mRNA up-regulation). Trolox completely prevented the induction of NRF2, SOD1 and catalase mRNAs, but not atrophy or induction of catabolic systems in unloaded muscles, suggesting that oxidative stress is not a major cause of disuse atrophy. HU mice showed a marked alteration of oxidative metabolism. PGC-1α and mitochondrial complexes were down-regulated and DRP1 was up-regulated. To define the link between mitochondrial dysfunction and disuse muscle atrophy we unloaded mice overexpressing PGC-1α. Transgenic PGC-1α animals did not show metabolic alteration during unloading, preserving muscle size through the reduction of autophagy and proteasome degradation. Our results indicate that mitochondrial dysfunction plays a major role in disuse atrophy and that compounds inducing PGC-1α expression could be useful to treat/prevent muscle atrophy. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  14. PGC1-α over-expression prevents metabolic alterations and soleus muscle atrophy in hindlimb unloaded mice

    PubMed Central

    Cannavino, Jessica; Brocca, Lorenza; Sandri, Marco; Bottinelli, Roberto; Pellegrino, Maria Antonietta

    2014-01-01

    Prolonged skeletal muscle inactivity causes muscle fibre atrophy. Redox imbalance has been considered one of the major triggers of skeletal muscle disuse atrophy, but whether redox imbalance is actually the major cause or simply a consequence of muscle disuse remains of debate. Here we hypothesized that a metabolic stress mediated by PGC-1α down-regulation plays a major role in disuse atrophy. First we studied the adaptations of soleus to mice hindlimb unloading (HU) in the early phase of disuse (3 and 7 days of HU) with and without antioxidant treatment (trolox). HU caused a reduction in cross-sectional area, redox status alteration (NRF2, SOD1 and catalase up-regulation), and induction of the ubiquitin proteasome system (MuRF-1 and atrogin-1 mRNA up-regulation) and autophagy (Beclin1 and p62 mRNA up-regulation). Trolox completely prevented the induction of NRF2, SOD1 and catalase mRNAs, but not atrophy or induction of catabolic systems in unloaded muscles, suggesting that oxidative stress is not a major cause of disuse atrophy. HU mice showed a marked alteration of oxidative metabolism. PGC-1α and mitochondrial complexes were down-regulated and DRP1 was up-regulated. To define the link between mitochondrial dysfunction and disuse muscle atrophy we unloaded mice overexpressing PGC-1α. Transgenic PGC-1α animals did not show metabolic alteration during unloading, preserving muscle size through the reduction of autophagy and proteasome degradation. Our results indicate that mitochondrial dysfunction plays a major role in disuse atrophy and that compounds inducing PGC-1α expression could be useful to treat/prevent muscle atrophy. PMID:25128574

  15. Oxidation of the skeletal muscle Ca2+ release channel alters calmodulin binding

    NASA Technical Reports Server (NTRS)

    Zhang, J. Z.; Wu, Y.; Williams, B. Y.; Rodney, G.; Mandel, F.; Strasburg, G. M.; Hamilton, S. L.

    1999-01-01

    This study presents evidence for a close relationship between the oxidation state of the skeletal muscle Ca2+ release channel (RyR1) and its ability to bind calmodulin (CaM). CaM enhances the activity of RyR1 in low Ca2+ and inhibits its activity in high Ca2+. Oxidation, which activates the channel, blocks the binding of 125I-labeled CaM at both micromolar and nanomolar Ca2+ concentrations. Conversely, bound CaM slows oxidation-induced cross-linking between subunits of the RyR1 tetramer. Alkylation of hyperreactive sulfhydryls (<3% of the total sulfhydryls) on RyR1 with N-ethylmaleimide completely blocks oxidant-induced intersubunit cross-linking and inhibits Ca2+-free 125I-CaM but not Ca2+/125I-CaM binding. These studies suggest that 1) the sites on RyR1 for binding apocalmodulin have features distinct from those of the Ca2+/CaM site, 2) oxidation may alter the activity of RyR1 in part by altering its interaction with CaM, and 3) CaM may protect RyR1 from oxidative modifications during periods of oxidative stress.

  16. Mechanisms by which smooth muscle sensitivity may be altered by calcium.

    PubMed

    Kaiman, M; Shibata, S

    1978-01-01

    6-Hydroxydopamine (6-OHDA) increased the sensitivity of rat, rabbit and guinea pig portal veins to norepinephrine (NE), methoxamine (ME), barium (Ba++) and calcium (Ca++) but not to potassium (K+). Reserpine potentiated the responses of NE, ME and Ca++ but not Ba++ or K+ in rabbit and guinea pig veins and did not alter the sensitivity of rat veins to all agonists tested. Cocaine only potentiated the NE responses of the veins and decreased the sensitivity of rabbit and guinea pig veins to K+. 6-OHDA increased 48Ca-influx in all veins whereas reserpine increased 45Ca-influx only in rabbit and guinea pig veins. Cocaine failed to increase 45Ca-influx in all veins tested. NE, ME and K+ increased 45Ca-influx in the veins from the different animals. The agonist-induced 45Ca-influx was greater in most of the supersensitive veins than in the control veins. In veins that failed to develop supersensitivity, agonist-induced 45Ca-influx did not differ from that of the control veins. It is concluded that the development of super- and subsensitivity exhibits species variation and that the alteration in Ca++ influx would be consistent with the changes in sensitivity of the venous smooth muscle.

  17. Oxidation of the skeletal muscle Ca2+ release channel alters calmodulin binding

    NASA Technical Reports Server (NTRS)

    Zhang, J. Z.; Wu, Y.; Williams, B. Y.; Rodney, G.; Mandel, F.; Strasburg, G. M.; Hamilton, S. L.

    1999-01-01

    This study presents evidence for a close relationship between the oxidation state of the skeletal muscle Ca2+ release channel (RyR1) and its ability to bind calmodulin (CaM). CaM enhances the activity of RyR1 in low Ca2+ and inhibits its activity in high Ca2+. Oxidation, which activates the channel, blocks the binding of 125I-labeled CaM at both micromolar and nanomolar Ca2+ concentrations. Conversely, bound CaM slows oxidation-induced cross-linking between subunits of the RyR1 tetramer. Alkylation of hyperreactive sulfhydryls (<3% of the total sulfhydryls) on RyR1 with N-ethylmaleimide completely blocks oxidant-induced intersubunit cross-linking and inhibits Ca2+-free 125I-CaM but not Ca2+/125I-CaM binding. These studies suggest that 1) the sites on RyR1 for binding apocalmodulin have features distinct from those of the Ca2+/CaM site, 2) oxidation may alter the activity of RyR1 in part by altering its interaction with CaM, and 3) CaM may protect RyR1 from oxidative modifications during periods of oxidative stress.

  18. Rapid loss of adiponectin-stimulated fatty acid oxidation in skeletal muscle of rats fed a high fat diet is not due to altered muscle redox state.

    PubMed

    Ritchie, Ian R W; Dyck, David J

    2012-01-01

    A high fat (HF) diet rapidly impairs the ability of adiponectin (Ad) to stimulate fatty acid (FA) oxidation in oxidative soleus muscle, but the underlying mechanism remains elusive. Mere days of HF feeding also increase the muscle's production and accumulation of reactive oxygen species (ROS) and shift cellular redox to a more oxidized state. It seems plausible that this shift towards a more oxidized state might act as negative feedback to suppress the ability of Ad to stimulate FA oxidation and generate more ROS. Therefore, we sought to determine whether i) a shift towards a more oxidized redox state (reduction in GSH/2GSSG) coincided with impaired Ad-stimulated palmitate oxidation in oxidative and glycolytic rodent muscle after 5 days of HF feeding (60% kCal), and ii) if supplementation with the antioxidant, N-acetylcysteine (NAC) could prevent the HF-diet induced impairment in Ad-response. Globular Ad (gAd) increased palmitate oxidation in isolated soleus and EDL muscles by 42% and 34%, respectively (p<0.05) but this was attenuated with HF feeding in both muscles. HF feeding decreased total GSH (-26%, p<0.05) and GSH/2GSSG (-49%, p<0.05) in soleus, but not EDL. Supplementation with NAC prevented the HF diet-induced reductions in GSH and GSH/2GSSG in soleus, but did not prevent the loss of Ad response in either muscle. Furthermore, direct incubations with H(2)O(2) did not impair Ad-stimulated FA oxidation in either muscle. In conclusion, our data indicates that skeletal muscle Ad resistance is rapidly induced in both oxidative and glycolytic muscle, independently of altered cellular redox state.

  19. Vascular smooth muscle cell alterations triggered by mice adipocytes: role of high-fat diet.

    PubMed

    El Akoum, Souhad; Cloutier, Isabelle; Tanguay, Jean-François

    2012-01-01

    Inherent mechanisms leading to vascular smooth muscle cells (VSMC) alterations in obesitylinked type 2 diabetes (T2D) situation remain to be clarified. This study evaluates the impact of supernatant of adipocytes extracted from mice fed high-fat-diets (HFD) on the proliferation and apoptosis of VSMC. Adipocytes were extracted from visceral white fat pads of male and female C57Bl6 mice showing different stages of metabolic alterations after 20 weeks of vegetal or animal HFD feeding. These cells were stimulated or not with insulin or glucose to condition VSMC media. After 24h of stimulation with adipocyte supernatants (AdS), VSMC proliferation and sustainability were assessed in the absence and presence of AdS. CD36 and insulin receptor mRNA levels were also evaluated. Proliferation and viability of VSMC were significantly modulated by the nature of the AdS used and the gender of mice from which adipocytes have been extracted. The most extensive effects on VSMC were triggered by adipocytes from males fed animal HFD and females fed vegetal HFD. These effects were concurrent with increased leptin concentration and decreased adiponectin levels in AdS. In addition, adipocytes of HFD-fed mice increased caspase-3 activity and apoptosis in VSMC. Significant up-regulation of CD36 mRNA was also found in these cells. Adipocytes of HFD-fed mice induce VSMC alterations. These changes involved mouse gender, most probably correlated to the diet-induced adipocyte secretion profile. Greater sensitivity to AdS effects in VSMC raises concerns about the more frequent cardiovascular events associated with obesity in the presence of T2D, which impairs adipocyte activity.

  20. Alterations in Notch signalling in skeletal muscles from mdx and dko dystrophic mice and patients with Duchenne muscular dystrophy.

    PubMed

    Church, Jarrod E; Trieu, Jennifer; Chee, Annabel; Naim, Timur; Gehrig, Stefan M; Lamon, Séverine; Angelini, Corrado; Russell, Aaron P; Lynch, Gordon S

    2014-04-01

    New Findings What is the central question of this study? The Notch signalling pathway plays an important role in muscle regeneration, and activation of the pathway has been shown to enhance muscle regeneration in aged mice. It is unknown whether Notch activation will have a similarly beneficial effect on muscle regeneration in the context of Duchenne muscular dystrophy (DMD). What is the main finding and its importance? Although expression of Notch signalling components is altered in both mouse models of DMD and in human DMD patients, activation of the Notch signalling pathway does not confer any functional benefit on muscles from dystrophic mice, suggesting that other signalling pathways may be more fruitful targets for manipulation in treating DMD. Abstract In Duchenne muscular dystrophy (DMD), muscle damage and impaired regeneration lead to progressive muscle wasting, weakness and premature death. The Notch signalling pathway represents a central regulator of gene expression and is critical for cellular proliferation, differentiation and apoptotic signalling during all stages of embryonic muscle development. Notch activation improves muscle regeneration in aged mice, but its potential to restore regeneration and function in muscular dystrophy is unknown. We performed a comprehensive examination of several genes involved in Notch signalling in muscles from dystrophin-deficient mdx and dko (utrophin- and dystrophin-null) mice and DMD patients. A reduction of Notch1 and Hes1 mRNA in tibialis anterior muscles of dko mice and quadriceps muscles of DMD patients and a reduction of Hes1 mRNA in the diaphragm of the mdx mice were observed, with other targets being inconsistent across species. Activation and inhibition of Notch signalling, followed by measures of muscle regeneration and function, were performed in the mouse models of DMD. Notch activation had no effect on functional regeneration in C57BL/10, mdx or dko mice. Notch inhibition significantly depressed the

  1. A High-Fat High-Sucrose Diet Rapidly Alters Muscle Integrity, Inflammation and Gut Microbiota in Male Rats

    PubMed Central

    Collins, Kelsey H.; Paul, Heather A.; Hart, David A.; Reimer, Raylene A.; Smith, Ian C.; Rios, Jaqueline L.; Seerattan, Ruth A.; Herzog, Walter

    2016-01-01

    The chronic low-level inflammation associated with obesity is known to deleteriously affect muscle composition. However, the manner in which obesity leads to muscle loss has not been explored in detail or in an integrated manner following a short-term metabolic challenge. In this paper, we evaluated the relationships between compromised muscle integrity, diet, systemic inflammatory mediators, adipose tissue, and gut microbiota in male Sprague-Dawley rats. We show that intramuscular fat, fibrosis, and the number of pro-inflammatory cells increased by 3-days and was sustained across 28-days of high-fat high-sugar feeding compared to control-diet animals. To understand systemic contributors to muscle damage, dynamic changes in gut microbiota and serum inflammatory markers were evaluated. Data from this study links metabolic challenge to persistent compromise in muscle integrity after just 3-days, a finding associated with altered gut microbiota and systemic inflammatory changes. These data contribute to our understanding of early consequences of metabolic challenge on multiple host systems, which are important to understand as obesity treatment options are developed. Therefore, intervention within this early period of metabolic challenge may be critical to mitigate these sustained alterations in muscle integrity. PMID:27853291

  2. Mitochondrial alterations and oxidative stress in an acute transient mouse model of muscle degeneration: implications for muscular dystrophy and related muscle pathologies.

    PubMed

    Ramadasan-Nair, Renjini; Gayathri, Narayanappa; Mishra, Sudha; Sunitha, Balaraju; Mythri, Rajeswara Babu; Nalini, Atchayaram; Subbannayya, Yashwanth; Harsha, Hindalahalli Chandregowda; Kolthur-Seetharam, Ullas; Srinivas Bharath, Muchukunte Mukunda

    2014-01-03

    Muscular dystrophies (MDs) and inflammatory myopathies (IMs) are debilitating skeletal muscle disorders characterized by common pathological events including myodegeneration and inflammation. However, an experimental model representing both muscle pathologies and displaying most of the distinctive markers has not been characterized. We investigated the cardiotoxin (CTX)-mediated transient acute mouse model of muscle degeneration and compared the cardinal features with human MDs and IMs. The CTX model displayed degeneration, apoptosis, inflammation, loss of sarcolemmal complexes, sarcolemmal disruption, and ultrastructural changes characteristic of human MDs and IMs. Cell death caused by CTX involved calcium influx and mitochondrial damage both in murine C2C12 muscle cells and in mice. Mitochondrial proteomic analysis at the initial phase of degeneration in the model detected lowered expression of 80 mitochondrial proteins including subunits of respiratory complexes, ATP machinery, fatty acid metabolism, and Krebs cycle, which further decreased in expression during the peak degenerative phase. The mass spectrometry (MS) data were supported by enzyme assays, Western blot, and histochemistry. The CTX model also displayed markers of oxidative stress and a lowered glutathione reduced/oxidized ratio (GSH/GSSG) similar to MDs, human myopathies, and neurogenic atrophies. MS analysis identified 6 unique oxidized proteins from Duchenne muscular dystrophy samples (n = 6) (versus controls; n = 6), including two mitochondrial proteins. Interestingly, these mitochondrial proteins were down-regulated in the CTX model thereby linking oxidative stress and mitochondrial dysfunction. We conclude that mitochondrial alterations and oxidative damage significantly contribute to CTX-mediated muscle pathology with implications for human muscle diseases.

  3. Endocrine alterations from concentric vs. eccentric muscle actions: a brief review.

    PubMed

    Kraemer, Robert R; Castracane, V Daniel

    2015-02-01

    Resistance exercise has a positive effect on many tissues, including heart, bone, skeletal muscle, and nervous tissue. Eccentric muscle actions offer a unique and a potentially beneficial form of exercise for maintaining and improving health. During resistance exercise, the effects of gravity, and mechanical properties of the sarcomere and connective tissue in skeletal muscle allow a greater muscle load during an eccentric (lengthening) muscle contraction than a concentric (shortening) muscle contraction. Consequently, older patients, patients with muscle or limb movement limitations or injuries, as well as cancer patients may be able to benefit from isolated eccentric muscle actions. There are specific physiological responses to eccentric muscle contractions. This review will describe the effects of different eccentric muscle contraction protocols on endocrine responses that could have positive effects on different tissues and recommend direction for future research.

  4. Carbohydrate Analysis

    NASA Astrophysics Data System (ADS)

    Bemiller, James N.

    Carbohydrates are important in foods as a major source of energy, to impart crucial textural properties, and as dietary fiber which influences physiological processes. Digestible carbohydrates, which are converted into monosaccharides, which are absorbed, provide metabolic energy. Worldwide, carbohydrates account for more than 70% of the caloric value of the human diet. It is recommended that all persons should limit calories from fat (the other significant source) to not more than 30% and that most of the carbohydrate calories should come from starch. Nondigestible polysaccharides (all those other than starch) comprise the major portion of dietary fiber (Sect. 10.5). Carbohydrates also contribute other attributes, including bulk, body, viscosity, stability to emulsions and foams, water-holding capacity, freeze-thaw stability, browning, flavors, aromas, and a range of desirable textures (from crispness to smooth, soft gels). They also provide satiety. Basic carbohydrate structures, chemistry, and terminology can be found in references (1, 2).

  5. Carbohydrate bioavailability.

    PubMed

    Englyst, Klaus N; Englyst, Hans N

    2005-07-01

    There is consensus that carbohydrate foods, in the form of fruit, vegetables and whole-grain products, are beneficial to health. However, there are strong indications that highly processed, fibre-depleted, and consequently rapidly digestible, energy-dense carbohydrate food products can lead to over-consumption and obesity-related diseases. Greater attention needs to be given to carbohydrate bioavailability, which is determined by the chemical identity and physical form of food. The objective of the present concept article is to provide a rational basis for the nutritional characterisation of dietary carbohydrates. Based on the properties of carbohydrate foods identified to be of specific relevance to health, we propose a classification and measurement scheme that divides dietary carbohydrates into glycaemic carbohydrates (digested and absorbed in the small intestine) and non-glycaemic carbohydrates (enter the large intestine). The glycaemic carbohydrates are characterised by sugar type, and by the likely rate of digestion described by in vitro measurements for rapidly available glucose and slowly available glucose. The main type of non-glycaemic carbohydrates is the plant cell-wall NSP, which is a marker of the natural fibre-rich diet recognised as beneficial to health. Other non-glycaemic carbohydrates include resistant starch and the resistant short-chain carbohydrates (non-digestible oligosaccharides), which should be measured and researched in their own right. The proposed classification and measurement scheme is complementary to the dietary fibre and glycaemic index concepts in the promotion of healthy diets with low energy density required for combating obesity-related diseases.

  6. Streptococcus iniae cpsG alters capsular carbohydrate composition and is a cause of serotype switching in vaccinated fish.

    PubMed

    Heath, Candice; Gillen, Christine M; Chrysanthopoulos, Panagiotis; Walker, Mark J; Barnes, Andrew C

    2016-09-25

    Streptococcus iniae causes septicaemia and meningitis in marine and freshwater fish wherever they are farmed in warm-temperate and tropical regions. Although serotype specific, vaccination with bacterins (killed bacterial cultures) is largely successful and vaccine failure occurs only occasionally through emergence of new capsular serotypes. Previously we showed that mutations in vaccine escapes are restricted to a limited repertoire of genes within the 20-gene capsular polysaccharide (cps) operon. cpsG, a putative UDP-galactose 4-epimerase, has three sequence types based on the insertion or deletion of the three amino acids leucine, serine and lysine in the substrate binding site of the protein. To elucidate the role of cpsG in capsular polysaccharide (CPS) biosynthesis and capsular composition, we first prepared isogenic knockout and complemented mutants of cpsG by allelic exchange mutagenesis. Deletion of cpsG resulted in changes to colony morphology and cell buoyant density, and also significantly decreased galactose content relative to glucose in the capsular polysaccharide as determined by GC-MS, consistent with epimerase activity of CpsG. There was also a metabolic penalty of cpsG knockout revealed by slower growth in complex media, and reduced proliferation in whole fish blood. Moreover, whilst antibodies raised in fish against the wild type cross-reacted in whole cell and cps ELISA, they did not cross-opsonise the mutant in a peripheral blood neutrophil opsonisation assay, consistent with reported vaccine escape. We have shown here that mutation in cpsG results in altered CPS composition and this in turn results in poor cross-opsonisation that explains some of the historic vaccination failure on fish farms in Australia.

  7. Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy.

    PubMed

    Fugier, Charlotte; Klein, Arnaud F; Hammer, Caroline; Vassilopoulos, Stéphane; Ivarsson, Ylva; Toussaint, Anne; Tosch, Valérie; Vignaud, Alban; Ferry, Arnaud; Messaddeq, Nadia; Kokunai, Yosuke; Tsuburaya, Rie; de la Grange, Pierre; Dembele, Doulaye; Francois, Virginie; Precigout, Guillaume; Boulade-Ladame, Charlotte; Hummel, Marie-Christine; Lopez de Munain, Adolfo; Sergeant, Nicolas; Laquerrière, Annie; Thibault, Christelle; Deryckere, François; Auboeuf, Didier; Garcia, Luis; Zimmermann, Pascale; Udd, Bjarne; Schoser, Benedikt; Takahashi, Masanori P; Nishino, Ichizo; Bassez, Guillaume; Laporte, Jocelyn; Furling, Denis; Charlet-Berguerand, Nicolas

    2011-06-01

    Myotonic dystrophy is the most common muscular dystrophy in adults and the first recognized example of an RNA-mediated disease. Congenital myotonic dystrophy (CDM1) and myotonic dystrophy of type 1 (DM1) or of type 2 (DM2) are caused by the expression of mutant RNAs containing expanded CUG or CCUG repeats, respectively. These mutant RNAs sequester the splicing regulator Muscleblind-like-1 (MBNL1), resulting in specific misregulation of the alternative splicing of other pre-mRNAs. We found that alternative splicing of the bridging integrator-1 (BIN1) pre-mRNA is altered in skeletal muscle samples of people with CDM1, DM1 and DM2. BIN1 is involved in tubular invaginations of membranes and is required for the biogenesis of muscle T tubules, which are specialized skeletal muscle membrane structures essential for excitation-contraction coupling. Mutations in the BIN1 gene cause centronuclear myopathy, which shares some histopathological features with myotonic dystrophy. We found that MBNL1 binds the BIN1 pre-mRNA and regulates its alternative splicing. BIN1 missplicing results in expression of an inactive form of BIN1 lacking phosphatidylinositol 5-phosphate-binding and membrane-tubulating activities. Consistent with a defect of BIN1, muscle T tubules are altered in people with myotonic dystrophy, and membrane structures are restored upon expression of the normal splicing form of BIN1 in muscle cells of such individuals. Finally, reproducing BIN1 splicing alteration in mice is sufficient to promote T tubule alterations and muscle weakness, a predominant feature of myotonic dystrophy.

  8. Aging is associated with altered vasodilator kinetics in dynamically contracting muscle: role of nitric oxide

    PubMed Central

    Ranadive, Sushant M.; Joyner, Michael J.

    2015-01-01

    We tested the hypothesis that aging would be associated with slowed vasodilator kinetics in contracting muscle in part due to a reduced nitric oxide (NO) bioavailability. Young (n = 10; 24 ± 2 yr) and older (n = 10; 67 ± 2 yr) adults performed rhythmic forearm exercise (4 min each) at 10, 20, and 30% of max during saline infusion (control) and NO synthase (NOS) inhibition. Brachial artery diameter and velocities were measured using Doppler ultrasound. Forearm vascular conductance (FVC) was calculated for each duty cycle (1 s contraction/2 s relaxation) from forearm blood flow (FBF; ml/min) and blood pressure (mmHg) and fit with a monoexponential model. The main parameters derived from the model were the amplitude of the FBF and FVC response and the number of duty cycles for FBF and FVC to change 63% of the steady-state amplitude (τFBF and τFVC). Under control conditions 1) the amplitude of the FVC response at 30% maximal voluntary contraction (MVC) was lower in older compared with young adults (319 ± 33 vs. 462 ± 52 ml·min−1·100 mmHg−1; P < 0.05) and 2) τFVC was slower in older (10 ± 1, 13 ± 1, and 15 ± 1 duty cycles) compared with young (6 ± 1, 9 ± 1, and 11 ± 1 duty cycles) adults at all intensities (P < 0.05). In young adults, NOS inhibition blunted the amplitude of the FVC response at 30% MVC and prolonged the τFVC at all intensities (10 ± 2, 12 ± 1, and 16 ± 2 duty cycles; P < 0.05), whereas it did not change in older adults. Our data indicate that the blood flow and vasodilator kinetics in exercising muscle are altered with aging possibly due to blunted NO signaling. PMID:26023230

  9. Aging alters muscle reflex control of autonomic cardiovascular responses to rhythmic contractions in humans.

    PubMed

    Sidhu, Simranjit K; Weavil, Joshua C; Venturelli, Massimo; Rossman, Matthew J; Gmelch, Benjamin S; Bledsoe, Amber D; Richardson, Russell S; Amann, Markus

    2015-11-01

    We investigated the influence of aging on the group III/IV muscle afferents in the exercise pressor reflex-mediated cardiovascular response to rhythmic exercise. Nine old (OLD; 68 ± 2 yr) and nine young (YNG; 24 ± 2 yr) males performed single-leg knee extensor exercise (15 W, 30 W, 80% max) under control conditions and with lumbar intrathecal fentanyl impairing feedback from group III/IV leg muscle afferents. Mean arterial pressure (MAP), cardiac output, leg blood flow (QL), systemic (SVC) and leg vascular conductance (LVC) were continuously determined. With no hemodynamic effect at rest, fentanyl blockade during exercise attenuated both cardiac output and QL ∼17% in YNG, while the decrease in cardiac output in OLD (∼5%) was significantly smaller with no impact on QL (P = 0.8). Therefore, in the face of similar significant ∼7% reduction in MAP during exercise with fentanyl blockade in both groups, LVC significantly increased ∼11% in OLD, but decreased ∼8% in YNG. The opposing direction of change was reflected in SVC with a significant ∼5% increase in OLD and a ∼12% decrease in YNG. Thus while cardiac output seems to account for the majority of group III/IV-mediated MAP responses in YNG, the impact of neural feedback on the heart may decrease with age and alterations in SVC become more prominent in mediating the similar exercise pressor reflex in OLD. Interestingly, in terms of peripheral hemodynamics, while group III/IV-mediated feedback plays a clear role in increasing LVC during exercise in the YNG, these afferents seem to actually reduce LVC in OLD. These peripheral findings may help explain the limited exercise-induced peripheral vasodilation often associated with aging.

  10. Alterations in /sup 28/Mg binding in rabbit aortic smooth muscle

    SciTech Connect

    Weiss, G.B.; Shetty, S.S.

    1986-03-01

    The effects of various cations and drugs on /sup 28/Mg movements in the media-intimal layer of rabbit aorta were measured. Muscles were incubated with /sup 28/Mg for at least 90 min to assure sufficient accumulation. The /sup 28/Mg tissue/medium ratio was reduced by two-thirds in the presence of 1.5 mM (added) Mg/sup + +/. The rate of efflux of /sup 28/Mg was not altered by addition of non-radioactive Mg/sup + +/, Ca/sup + +/, Ga/sup + +/ or La/sup + + +/ during washout, but was increased by 0.5 mM EDTA. Uptake of /sup 28/Mg was inhibited substantially by added K/sup +/ (60 mM), neomycin (7 mM), genamicin (4.08 mg/ml), lidocaine (1 mM), Tris (substituted for Na/sup +/) and La/sup + + +/ (1.5 and 15 mM). Substitution of up to 75% of the NaCl present with sucrose resulted in a concentration-dependent increase in /sup 28/Mg uptake (up to more than 7-fold). A transient increase in /sup 28/Mg efflux rate was observed when muscles incubated in sucrose-substituted (for NaCl) Tris solution were exposed to Na/sup +/ (but not when Mg/sup + +/, Ca/sup + +/ or Ga/sup + +/ were added). The results indicate that cellular /sup 28/Mg is slowly accumulated and not readily exchanged. The interactions between NaCl and /sup 28/Mg may involve either an inhibition of Mg/sup + +/ uptake or an enhancement of Mg/sup + +/ efflux in the presence of extracellular NaCl.

  11. Altered carbohydrate metabolism in the storage roots of sweet potato plants overexpressing the SRF1 gene, which encodes a Dof zinc finger transcription factor.

    PubMed

    Tanaka, Masaru; Takahata, Yasuhiro; Nakayama, Hiroki; Nakatani, Makoto; Tahara, Makoto

    2009-09-01

    In order to characterize the functions of the sweetpotato SRF1 gene, which encodes a Dof zinc finger transcriptional factor preferentially expressed in the storage roots, we isolated its full length cDNA and produced transgenic sweetpotato plants with altered SRF1 expression levels. The isolated cDNA of SRF1 encoded a polypeptide of 497 amino acids and was closely related to the cyclic Dof factors of Arabidopsis and the ascorbate oxidase binding protein of pumpkin. SRF1 was most highly expressed in storage roots, although some expression was also observed in other vegetative tissue. Transgenic plants overexpressing SRF1 showed significantly higher storage root dry matter content compared to the original cultivar Kokei No. 14 or control transgenic plants. In these plants, the starch content per fresh weight of the storage roots was also higher than that of the wild-type plants, while the glucose and fructose content drastically decreased. Among the enzymes involved in the sugar metabolism, soluble acid invertase showed a decreased activity in the transgenic plants. Gene expression analysis showed that the expression of Ibbetafruct2, which encodes an isoform of vacuolar invertase, was suppressed in the transgenic plants overexpressing the SRF1 gene. These data suggest that SRF1 modulates the carbohydrate metabolism in the storage roots through negative regulation of a vacuolar invertase gene.

  12. Altered expression of O-GlcNAc-modified proteins in a mouse model whose glycemic status is controlled by a low carbohydrate ketogenic diet.

    PubMed

    Okuda, Tetsuya; Fukui, Asami; Morita, Naoki

    2013-11-01

    Abnormal modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc) is known to be associated with the pathology induced by hyperglycemia. However, the dynamic mechanism of O-GlcNAc modification under hyperglycemic conditions in vivo has not been fully characterized. To understand the mechanism, we established an animal model in which the glycemic status is controlled by the diet. A mutant mouse (ob/ob) which exhibits diet-induced hyperglycemia when fed a regular chow (chow) was used to establish this model; the mice were fed a very low carbohydrate ketogenic diet (KD) to improve hyperglycemia. Using this model, we evaluated the levels of O-GlcNAc-modified proteins in tissues under a hyperglycemic or its improved condition. ELISA and Western blot analyses revealed that altered expression of certain proteins modified by O-GlcNAc were found in the mice tissues, although global O-GlcNAc levels in the tissues remained unaltered by improvement of hyperglycemia. We also found the Akt protein kinase was modified by O-GlcNAc in the liver of ob/ob mice, and the modification levels were decreased by improvement of hyperglycemia. Furthermore, aberrant phosphorylation of Akt was found in the liver of ob/ob mice under hyperglycemic condition. In conclusion, our established mouse model is useful for evaluating the dynamics of O-GlcNAc-modified proteins in tissues associated with glycemic status. This study revealed that the expression level of certain proteins modified by O-GlcNAc is altered when KD improves the hyperglycemia. These proteins could be prospective indexes for nutritional therapy for hyperglycemia-associated diseases, such as diabetes mellitus.

  13. Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose.

    PubMed

    Goossens, Gijs H; Moors, Chantalle C M; Jocken, Johan W E; van der Zijl, Nynke J; Jans, Anneke; Konings, Ellen; Diamant, Michaela; Blaak, Ellen E

    2016-03-14

    Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [²H₂]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-(13)C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects.

  14. Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose

    PubMed Central

    Goossens, Gijs H.; Moors, Chantalle C. M.; Jocken, Johan W. E.; van der Zijl, Nynke J.; Jans, Anneke; Konings, Ellen; Diamant, Michaela; Blaak, Ellen E.

    2016-01-01

    Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-13C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects. PMID:26985905

  15. Alterations to mTORC1 signaling in the skeletal muscle differentially affect whole-body metabolism.

    PubMed

    Guridi, Maitea; Kupr, Barbara; Romanino, Klaas; Lin, Shuo; Falcetta, Denis; Tintignac, Lionel; Rüegg, Markus A

    2016-01-01

    The mammalian target of rapamycin complex 1 (mTORC1) is a central node in a network of signaling pathways controlling cell growth and survival. This multiprotein complex integrates external signals and affects different nutrient pathways in various organs. However, it is not clear how alterations of mTORC1 signaling in skeletal muscle affect whole-body metabolism. We characterized the metabolic phenotype of young and old raptor muscle knock-out (RAmKO) and TSC1 muscle knock-out (TSCmKO) mice, where mTORC1 activity in skeletal muscle is inhibited or constitutively activated, respectively. Ten-week-old RAmKO mice are lean and insulin resistant with increased energy expenditure, and they are resistant to a high-fat diet (HFD). This correlates with an increased expression of histone deacetylases (HDACs) and a downregulation of genes involved in glucose and fatty acid metabolism. Ten-week-old TSCmKO mice are also lean, glucose intolerant with a decreased activation of protein kinase B (Akt/PKB) targets that regulate glucose transporters in the muscle. The mice are resistant to a HFD and show reduced accumulation of glycogen and lipids in the liver. Both mouse models suffer from a myopathy with age, with reduced fat and lean mass, and both RAmKO and TSCmKO mice develop insulin resistance and increased intramyocellular lipid content. Our study shows that alterations of mTORC1 signaling in the skeletal muscle differentially affect whole-body metabolism. While both inhibition and constitutive activation of mTORC1 induce leanness and resistance to obesity, changes in the metabolism of muscle and peripheral organs are distinct. These results indicate that a balanced mTORC1 signaling in the muscle is required for proper metabolic homeostasis.

  16. Absence of calf muscle metabolism alterations in active cystic fibrosis adults with mild to moderate lung disease.

    PubMed

    Decorte, N; Gruet, M; Camara, B; Quetant, S; Mely, L; Vallier, J M; Verges, S; Wuyam, B

    2017-01-01

    Specific alterations in skeletal muscle related to genetic defects may be present in adults with cystic fibrosis (CF). Limb muscle dysfunction may contribute to physical impairment in CF. We hypothesized that adults with CF would have altered calf muscle metabolism during exercise. Fifteen adults with CF and fifteen healthy controls matched for age, gender and physical activity performed a maximal cycling test and an evaluation of calf muscle energetics by (31)P magnetic resonance spectroscopy before, during and after plantar flexions to exhaustion. Maximal cycling test revealed lower exercise capacities in CF (VO2peak 2.44±0.11 vs. 3.44±0.23L·Min(-1), P=0.03). At rest, calf muscle phosphorus metabolites and pHi were similar in CF and controls (P>0.05). Maximal power output during plantar flexions was significantly lower in CF compared to controls (7.8±1.2 vs. 6.6±2.4W; P=0.013). At exhaustion, PCr concentration was similarly reduced in both groups (CF -33±7%, controls -34±6%, P=0.44), while PCr degradation at identical absolute workload was greater in CF patients (P=0.04). These differences disappeared when power output was normalized for differences in calf size (maximal power output: 0.10±0.02 vs. 0.10±0.03W/cm(2); P=0.87). Pi/PCr ratio and pHi during exercise as well as PCr recovery after exercise were similar between groups. Similar metabolic calf muscle responses during exercise and recovery were found in CF adults and controls. Overall, muscle anabolism rather than specific metabolic dysfunction may be critical regarding muscle function in CF. Copyright © 2016. Published by Elsevier B.V.

  17. Alterations in 18F-FDG accumulation into neck-related muscles after neck dissection for patients with oral cancers

    PubMed Central

    Kito, Shinji; Koga, Hirofumi; Kodama, Masaaki; Habu, Manabu; Kokuryo, Shinya; Oda, Masafumi; Matsuo, Kou; Nishino, Takanobu; Matsumoto-Takeda, Shinobu; Uehara, Masataka; Yoshiga, Daigo; Tanaka, Tatsurou; Nishimura, Shun; Miyamoto, Ikuya; Sasaguri, Masaaki; Tominaga, Kazuhiro; Yoshioka, Izumi; Morimoto, Yasuhiro

    2016-01-01

    Background 18F-fluoro-2-deoxy-D-glucose (18F-FDG) accumulations are commonly seen in the neck-related muscles of the surgical and non-surgical sides after surgery with neck dissection (ND) for oral cancers, which leads to radiologists having difficulty in diagnosing the lesions. To examine the alterations in 18F-FDG accumulation in neck-related muscles of patients after ND for oral cancer. Material and Methods 18F-FDG accumulations on positron emission tomography (PET)-computed tomography (CT) in neck-related muscles were retrospectively analyzed after surgical dissection of cervical lymph nodes in oral cancers. Results According to the extent of ND of cervical lymph nodes, the rate of patients with 18F-FDG-PET-positive areas increased in the trapezius, sternocleidomastoid, and posterior neck muscles of the surgical and/or non-surgical sides. In addition, SUVmax of 18F-FDG-PET-positive areas in the trapezius and sternocleidomastoid muscles were increased according to the extent of the ND. Conclusions In evaluating 18F-FDG accumulations after ND for oral cancers, we should pay attention to the 18F-FDG distributions in neck-related muscles including the non-surgical side as false-positive findings. Key words:18F-FDG, PET-CT, oral cancers, muscles. PMID:27031062

  18. Exercise-Induced Alterations in Skeletal Muscle, Heart, Liver, and Serum Metabolome Identified by Non-Targeted Metabolomics Analysis.

    PubMed

    Starnes, Joseph W; Parry, Traci L; O'Neal, Sara K; Bain, James R; Muehlbauer, Michael J; Honcoop, Aubree; Ilaiwy, Amro; Christopher, Peter M; Patterson, Cam; Willis, Monte S

    2017-08-08

    The metabolic and physiologic responses to exercise are increasingly interesting, given that regular physical activity enhances antioxidant capacity, improves cardiac function, and protects against type 2 diabetes. The metabolic interactions between tissues and the heart illustrate a critical cross-talk we know little about. To better understand the metabolic changes induced by exercise, we investigated skeletal muscle (plantaris, soleus), liver, serum, and heart from exercise trained (or sedentary control) animals in an established rat model of exercise-induced aerobic training via non-targeted GC-MS metabolomics. Exercise-induced alterations in metabolites varied across tissues, with the soleus and serum affected the least. The alterations in the plantaris muscle and liver were most alike, with two metabolites increased in each (citric acid/isocitric acid and linoleic acid). Exercise training additionally altered nine other metabolites in the plantaris (C13 hydrocarbon, inosine/adenosine, fructose-6-phosphate, glucose-6-phosphate, 2-aminoadipic acid, heptadecanoic acid, stearic acid, alpha-tocopherol, and oleic acid). In the serum, we identified significantly decreased alpha-tocopherol levels, paralleling the increases identified in plantaris muscle. Eleven unique metabolites were increased in the heart, which were not affected in the other compartments (malic acid, serine, aspartic acid, myoinositol, glutamine, gluconic acid-6-phosphate, glutamic acid, pyrophosphate, campesterol, phosphoric acid, creatinine). These findings complement prior studies using targeted metabolomics approaches to determine the metabolic changes in exercise-trained human skeletal muscle. Specifically, exercise trained vastus lateralus biopsies had significantly increased linoleic acid, oleic acid, and stearic acid compared to the inactive groups, which were significantly increased in plantaris muscle in the present study. While increases in alpha-tocopherol have not been identified in

  19. Type of carbohydrate in feed affects the expression of small leucine-rich proteoglycans (SLRPs), glycosaminoglycans (GAGs) and interleukins in skeletal muscle of Atlantic cod (Gadus morhua L.).

    PubMed

    Tingbø, M G; Pedersen, M E; Grøndahl, F; Kolset, S O; Veiseth-Kent, E; Enersen, G; Hannesson, K O

    2012-09-01

    Aquaculture requires feed that ensures rapid growth and healthy fish. Higher inclusion of plant ingredients is desirable, as marine resources are limited. In this study we investigated the effects of higher starch inclusion in feed on muscular extracellular matrix and interleukin expression in farmed cod. Starch was replaced by complex fibers in the low-starch diet to keep total carbohydrate inclusion similar. Blood glucose and fructosamine levels were elevated in the high-starch group. The group fed a high-starch diet showed up-regulation on mRNA level of proteoglycans biglycan and decorin. ELISA confirmed the real-time PCR results on protein level for biglycan and also showed increase of lumican. For decorin the protein levels were decreased in the high-starch group, in contrast to real-time PCR results. Disaccharide analyses using HPLC showed reduction of glycosaminoglycans. Further, there was up-regulation of interleukin-1β and -10 on mRNA level in muscle. This study shows that the muscular extracellular matrix composition is affected by diet, and that a high-starch diet results in increased expression of pro-inflammatory genes similar to diabetes in humans. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Alteration of Surface EMG amplitude levels of five major trunk muscles by defined electrode location displacement.

    PubMed

    Huebner, Agnes; Faenger, Bernd; Schenk, Philipp; Scholle, Hans-Christoph; Anders, Christoph

    2015-04-01

    Exact electrode positioning is vital for obtaining reliable results in Surface EMG. This study aimed at systematically assessing the influence of defined electrode shifts on measured Surface EMG amplitudes of trunk muscles in a group of 15 middle aged healthy male subjects. The following leftsided muscles were investigated: rectus abdominis muscle, internal and external oblique abdominal muscles, lumbar multifidus muscle, and longissimus muscle. In addition to the recommended electrode positions, extra electrodes were placed parallel to these and along muscle fiber direction. Measurements were performed under isometric conditions in upright body position. Gradually changing, but defined loads were applied considering subject's upper body weight. For the abdominal muscles amplitude differences varied considerably depending on load level, magnitude, and direction. For both back muscles amplitudes dropped consistently but rather little for parallel electrode displacements. However, for the longissimus muscle a caudal electrode shift resulted in an amplitude increase of similar extent and independent from load level. Influence of electrode position variations can be proven for all trunk muscles but are more evident in abdominal than back muscles. Those muscle-specific effects confirm the necessity for an exact definition of electrode positioning to allow comparisons between individual subjects, groups of subjects, and studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Alterations of the In Vivo Torque-Velocity Relationship of Human Skeletal Muscle Following 30 Days Exposure to Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Dudley, Gary A.; Duvoisin, Marc R.; Convertino, Victor A.; Buchanan, Paul

    1989-01-01

    The purpose of this study was to examine the effect of 30 d of 6 deg headdown bedrest (BR) on the in vivo strength of skeletal muscle. Peak angle specific (0.78 rad below horizontal) torque of the knee extensor (KE) and flexor (KF) muscle groups of both limbs was assessed during unilateral efforts at four speeds (0.52, 1.74, 2.97 and 4.19 rad/s) during concentric and at three speeds (0.52, 1.74 and 2.97 rad/s) during eccentric actions. The average decrease (P less than 0.05) of peak angle specific torque directly post-BR for the KE across speeds of concentric and eccentric actions was about 19% (n = 7). Recovery for 30 d following BR markedly improved strength to about 92% (P greater than 0.05) of 'normal'. Strength of the KF was not altered (P greater than 0.05) by BR (about a 6% decrease independent of speed and type of muscle action). Changes of strength were not affected by the type or speed of muscle action. The results indicate that strength of ex-tensor more than of flexor muscle groups of the lower limb is decreased by 30 d of bedrest and that this response does not alter the nature of the in vivo torque-velocity relation.

  2. Neck muscle fatigue differentially alters scapular and humeral kinematics during humeral elevation in subclinical neck pain participants versus healthy controls.

    PubMed

    Zabihhosseinian, Mahboobeh; Holmes, Michael W R; Howarth, Samuel; Ferguson, Brad; Murphy, Bernadette

    2017-04-01

    Scapular orientation is highly dependent on axioscapular muscle function. This study examined the impact of neck muscle fatigue on scapular and humeral kinematics in participants with and without subclinical neck pain (SCNP) during humeral elevation. Ten SCNP and 10 control participants performed three unconstrained trials of dominant arm humeral elevation in the scapular plane to approximately 120 degrees before and after neck extensor muscle fatigue. Three-dimensional scapular and humeral kinematics were measured during the humeral elevation trials. Humeral elevation plane angle showed a significant interaction between groups (SCNP vs controls) and trial (pre- vs post-fatigue) (p=0.001). Controls began the unconstrained humeral elevation task after fatigue in a more abducted position, (p=0.002). Significant baseline differences in scapular rotation existed between the two groups (Posterior/Anterior tilt, p=0.04; Internal/External Rotation, p=0.001). SCNP contributed to altered scapular kinematics. Neck muscle fatigue influenced humeral kinematics in controls but not the SCNP group; suggesting that altered scapular motor control in the SCNP group resulted in an impaired adaption further to the neck muscle fatigue. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Alteration of the extracellular matrix of smooth muscle cells by ascorbate treatment.

    PubMed

    Barone, L M; Faris, B; Chipman, S D; Toselli, P; Oakes, B W; Franzblau, C

    1985-06-18

    The protein composition in the extracellular matrix of cultured neonatal rat aortic smooth muscle cells has been monitored over time in culture. The influence of ascorbate on insoluble elastin and collagen has been described. In the absence of ascorbate, the cells accumulate an insoluble elastin component which can account for as much as 50% of the total protein in the extracellular matrix. In the presence of ascorbate, the amount of insoluble collagen increases, while the insoluble elastin content is significantly less. When ascorbate conditions are varied at different times during the culture, the extracellular matrices are altered with respect to collagen and elastin ratios. The decrease in elastin accumulation in the presence of ascorbate may be explained by an overhydroxylation of tropoelastin. Approximately 1/3 of the prolyl residues in the soluble elastin fractions isolated from cultures grown in the presence of ascorbate are hydroxylated. Since the insoluble elastin accumulated in these cultures contain the unique lysine-derived cross-links in amounts comparable to aortic tissue, this culture system proves ideal for studying the influence of extracellular matrix elastin on cell growth and metabolism.

  4. Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells

    PubMed Central

    Osterlund, Kristen L.; Handa, Robert J.

    2010-01-01

    Both protective and nonprotective effects of androgens on the cardiovascular system have been reported. Our previous studies show that the potent androgen receptor (AR) agonist dihydrotestosterone (DHT) increases levels of the vascular inflammatory mediator cyclooxygenase (COX)-2 in rodent cerebral arteries independent of an inflammatory stimulus. Little is known about the effects of androgens on inflammation in human vascular tissues. Therefore, we tested the hypothesis that DHT alters COX-2 levels in the absence and presence of induced inflammation in primary human coronary artery smooth muscle cells (HCASMC). Furthermore, we tested the ancillary hypothesis that DHT's effects on COX-2 levels are AR-dependent. Cells were treated with DHT (10 nM) or vehicle for 6 h in the presence or absence of LPS or IL-1β. Similar to previous observations in rodent arteries, in HCASMC, DHT alone increased COX-2 levels compared with vehicle. This effect of DHT was attenuated in the presence of the AR antagonist bicalutamide. Conversely, in the presence of LPS or IL-1β, increases in COX-2 were attenuated by cotreatment with DHT. Bicalutamide did not affect this response, suggesting that DHT-induced decreases in COX-2 levels occur independent of AR stimulation. Thus we conclude that DHT differentially influences COX-2 levels under physiological and pathophysiological conditions in HCASMC. This effect of DHT on COX-2 involves AR-dependent and- independent mechanisms, depending on the physiological state of the cell. PMID:20103743

  5. Modifying the Dietary Carbohydrate-to-Protein Ratio Alters the Postprandial Macronutrient Oxidation Pattern in Liver of AMPK-Deficient Mice.

    PubMed

    Chalvon-Demersay, Tristan; Even, Patrick C; Chaumontet, Catherine; Piedcoq, Julien; Viollet, Benoit; Gaudichon, Claire; Tomé, Daniel; Foretz, Marc; Azzout-Marniche, Dalila

    2017-09-01

    Background: Hepatic AMP-activated kinase (AMPK) activity is sensitive to the dietary carbohydrate-to-protein ratio. However, the role of AMPK in metabolic adaptations to variations in dietary macronutrients remains poorly understood.Objective: The objective of this study was to determine the role of hepatic AMPK in the adaptation of energy metabolism in response to modulation of the dietary carbohydrate-to-protein ratio.Methods: Male 7-wk-old wild-type (WT) and liver AMPK-deficient (knockout) mice were fed either a normal-protein and normal-carbohydrate diet (NP-NC; 14% protein, 76% carbohydrate on an energy basis), a low-protein and high-carbohydrate diet (LP-HC; 5% protein, 85% carbohydrate), or a high-protein and low-carbohydrate diet (HP-LC; 55% protein, 35% carbohydrate) for 3 wk. During this period, after an overnight fast, metabolic parameters were measured and indirect calorimetry was performed in mice during the first hours after refeeding a 1-g calibrated meal of their own diet in order to investigate lipid and carbohydrate metabolism.Results: Knockout mice fed an LP-HC or HP-LC meal exhibited 24% and 8% lower amplitudes in meal-induced carbohydrate and lipid oxidation changes. By contrast, knockout mice fed an NP-NC meal displayed normal carbohydrate and lipid oxidation profiles. These mice exhibited a transient increase in hepatic triglycerides and a decrease in hepatic glycogen. These changes were associated with a 650% higher secretion of fibroblast growth factor 21 (FGF21) 2 h after refeeding.Conclusions: The consequences of hepatic AMPK deletion depend on the dietary carbohydrate-to-protein ratio. In mice fed the NP-NC diet, deletion of AMPK in the liver led to an adaptation of liver metabolism resulting in increased secretion of FGF21. These changes possibly compensated for the absence of hepatic AMPK, as these mice exhibited normal postprandial changes in carbohydrate and lipid oxidation. By contrast, in mice fed the LP-HC and HP-LC diets, the

  6. Exposure to Radiofrequency Radiation Emitted from Common Mobile Phone Jammers Alters the Pattern of Muscle Contractions: an Animal Model Study.

    PubMed

    Rafati, A; Rahimi, S; Talebi, A; Soleimani, A; Haghani, M; Mortazavi, S M J

    2015-09-01

    The rapid growth of wireless communication technologies has caused public concerns regarding the biological effects of electromagnetic radiations on human health. Some early reports indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians such as the alterations of the pattern of muscle extractions. This study is aimed at investigating the effects of exposure to radiofrequency (RF) radiation emitted from mobile phone jammers on the pulse height of contractions, the time interval between two subsequent contractions and the latency period of frog's isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz). Frogs were kept in plastic containers in a room. Animals in the jammer group were exposed to radiofrequency (RF) radiation emitted from a common Jammer at a distance of 1m from the jammer's antenna for 2 hours while the control frogs were only sham exposed. Then animals were sacrificed and isolated gastrocnemius muscles were exposed to on/off jammer radiation for 3 subsequent 10 minute intervals. Isolated gastrocnemius muscles were attached to the force transducer with a string. Using a PowerLab device (26-T), the pattern of muscular contractions was monitored after applying single square pulses of 1V (1 Hz) as stimuli. The findings of this study showed that the pulse height of muscle contractions could not be affected by the exposure to electromagnetic fields. However, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields. These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions.

  7. CD4+ T cells enhance the unloaded shortening velocity of airway smooth muscle by altering the contractile protein expression.

    PubMed

    Matusovsky, Oleg S; Nakada, Emily M; Kachmar, Linda; Fixman, Elizabeth D; Lauzon, Anne-Marie

    2014-07-15

    Abundant data indicate that pathogenesis in allergic airways disease is orchestrated by an aberrant T-helper 2 (Th2) inflammatory response. CD4(+) T cells have been localized to airway smooth muscle (ASM) in both human asthmatics and in rodent models of allergic airways disease, where they have been implicated in proliferative responses of ASM. Whether CD4(+) T cells also alter ASM contractility has not been addressed. We established an in vitro system to assess the ability of antigen-stimulated CD4(+) T cells to modify contractile responses of the Brown Norway rat trachealis muscle. Our data demonstrated that the unloaded velocity of shortening (Vmax) of ASM was significantly increased upon 24 h co-incubation with antigen-stimulated CD4(+) T cells, while stress did not change. Enhanced Vmax was dependent upon contact between the CD4(+) T cells and the ASM and correlated with increased levels of the fast (+)insert smooth muscle myosin heavy chain isoform. The levels of myosin light chain kinase and myosin light chain phosphorylation were also increased within the muscle. The alterations in mechanics and in the levels of contractile proteins were transient, both declining to control levels after 48 h of co-incubation. More permanent alterations in muscle phenotype might be attainable when several inflammatory cells and mediators interact together or after repeated antigenic challenges. Further studies will await new tissue culture methodologies that preserve the muscle properties over longer periods of time. In conclusion, our data suggest that inflammatory cells promote ASM hypercontractility in airway hyper-responsiveness and asthma.

  8. Exposure to Radiofrequency Radiation Emitted from Common Mobile Phone Jammers Alters the Pattern of Muscle Contractions: an Animal Model Study

    PubMed Central

    Rafati, A.; Rahimi, S.; Talebi, A.; Soleimani, A.; Haghani, M.; Mortazavi, S. M. J.

    2015-01-01

    Introduction The rapid growth of wireless communication technologies has caused public concerns regarding the biological effects of electromagnetic radiations on human health. Some early reports indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians such as the alterations of the pattern of muscle extractions. This study is aimed at investigating the effects of exposure to radiofrequency (RF) radiation emitted from mobile phone jammers on the pulse height of contractions, the time interval between two subsequent contractions and the latency period of frog’s isolated gastrocnemius muscle after stimulation with single square pulses of 1V (1 Hz). Materials and Methods Frogs were kept in plastic containers in a room. Animals in the jammer group were exposed to radiofrequency (RF) radiation emitted from a common Jammer at a distance of 1m from the jammer’s antenna for 2 hours while the control frogs were only sham exposed. Then animals were sacrificed and isolated gastrocnemius muscles were exposed to on/off jammer radiation for 3 subsequent 10 minute intervals. Isolated gastrocnemius muscles were attached to the force transducer with a string. Using a PowerLab device (26-T), the pattern of muscular contractions was monitored after applying single square pulses of 1V (1 Hz) as stimuli. Results The findings of this study showed that the pulse height of muscle contractions could not be affected by the exposure to electromagnetic fields. However, the latency period was effectively altered in RF-exposed samples. However, none of the experiments could show an alteration in the time interval between two subsequent contractions after exposure to electromagnetic fields. Conclusion These findings support early reports which indicated a wide variety of non-thermal effects of electromagnetic radiation on amphibians including the effects on the pattern of muscle extractions. PMID:26396969

  9. Carbohydrate intake and obesity.

    PubMed

    van Dam, R M; Seidell, J C

    2007-12-01

    The prevalence of obesity has increased rapidly worldwide and the importance of considering the role of diet in the prevention and treatment of obesity is widely acknowledged. This paper reviews data on the effects of dietary carbohydrates on body fatness. Does the composition of the diet as related to carbohydrates affect the likelihood of passive over-consumption and long-term weight change? In addition, methodological limitations of both observational and experimental studies of dietary composition and body weight are discussed. Carbohydrates are among the macronutrients that provide energy and can thus contribute to excess energy intake and subsequent weight gain. There is no clear evidence that altering the proportion of total carbohydrate in the diet is an important determinant of energy intake. However, there is evidence that sugar-sweetened beverages do not induce satiety to the same extent as solid forms of carbohydrate, and that increases in sugar-sweetened soft drink consumption are associated with weight gain. Findings from studies on the effect of the dietary glycemic index on body weight have not been consistent. Dietary fiber is associated with a lesser degree of weight gain in observational studies. Although it is difficult to establish with certainty that fiber rather than other dietary attributes are responsible, whole-grain cereals, vegetables, legumes and fruits seem to be the most appropriate sources of dietary carbohydrate.

  10. Detection of ultrastructural changes in genetically altered and exercised skeletal muscle using PS-OCT

    NASA Astrophysics Data System (ADS)

    Pasquesi, James J.; Schlachter, Simon C.; Boppart, Marni D.; Chaney, Eric; Kaufman, Stephen J.; Boppart, Stephen A.

    2006-02-01

    Birefringence of skeletal muscle has been associated with the ultrastructure of individual sarcomeres, specifically the arrangement of A-bands corresponding to the thick myosin filaments. Murine skeletal muscle (gastrocnemius) was imaged with a fiber-based PS-OCT imaging system to determine the level of birefringence present in the tissue under various conditions. In addition to muscle controls from wild-type mice, muscle from abnormal mice included: genetically-modified (mdx) mice which model human muscular dystrophy, transgenic mice exhibiting an overexpression of integrin (α7β1), and transgenic integrin (α7β1)knockout mice. Comparisons were also made between rested and exercised muscles to determine the effects of exercise on muscle birefringence for each of these normal and abnormal conditions. The PS-OCT images revealed that the presence of birefringence was similar in the rested muscle with dystrophy-like features (i.e., lacking the structural protein dystrophin - mdx) and in the integrin (α7β1)knockout muscle when compared to the normal (wild-type) control. However, exercising these abnormal muscle tissues drastically reduced the presence of birefringence detected by the PS-OCT system. The muscle exhibiting an overexpression of integrin (α7β1) remained heavily birefringent before and after exercise, similar to the normal (wild-type) muscle. These results suggest that there is a distinct relationship between the degree of birefringence detected using PS-OCT and the sarcomeric ultrastructure present within skeletal muscle.

  11. In situ macrophage phenotypic transition is affected by altered cellular composition prior to acute sterile muscle injury.

    PubMed

    Patsalos, Andreas; Pap, Attila; Varga, Tamas; Trencsenyi, Gyorgy; Contreras, Gerardo Alvarado; Garai, Ildiko; Papp, Zoltan; Dezso, Balazs; Pintye, Eva; Nagy, Laszlo

    2017-09-01

    The in situ phenotypic switch of macrophages is delayed in acute injury following irradiation. The combination of bone marrow transplantation and local muscle radiation protection allows for the identification of a myeloid cell contribution to tissue repair. PET-MRI allows monitoring of myeloid cell invasion and metabolism. Altered cellular composition prior to acute sterile injury affects the in situ phenotypic transition of invading myeloid cells to repair macrophages. There is reciprocal intercellular communication between local muscle cell compartments, such as PAX7 positive cells, and recruited macrophages during skeletal muscle regeneration. Skeletal muscle regeneration is a complex interplay between various cell types including invading macrophages. Their recruitment to damaged tissues upon acute sterile injuries is necessary for clearance of necrotic debris and for coordination of tissue regeneration. This highly dynamic process is characterized by an in situ transition of infiltrating monocytes from an inflammatory (Ly6C(high) ) to a repair (Ly6C(low) ) macrophage phenotype. The importance of the macrophage phenotypic shift and the cross-talk of the local muscle tissue with the infiltrating macrophages during tissue regeneration upon injury are not fully understood and their study lacks adequate methodology. Here, using an acute sterile skeletal muscle injury model combined with irradiation, bone marrow transplantation and in vivo imaging, we show that preserved muscle integrity and cell composition prior to the injury is necessary for the repair macrophage phenotypic transition and subsequently for proper and complete tissue regeneration. Importantly, by using a model of in vivo ablation of PAX7 positive cells, we show that this radiosensitive skeletal muscle progenitor pool contributes to macrophage phenotypic transition following acute sterile muscle injury. In addition, local muscle tissue radioprotection by lead shielding during irradiation preserves

  12. Castration differentially alters basal and leucine-stimulated tissue protein synthesis in skeletal muscle and adipose tissue.

    PubMed

    Jiao, Qianning; Pruznak, Anne M; Huber, Danuta; Vary, Thomas C; Lang, Charles H

    2009-11-01

    Reduced testosterone as a result of catabolic illness or aging is associated with loss of muscle and increased adiposity. We hypothesized that these changes in body composition occur because of altered rates of protein synthesis under basal and nutrient-stimulated conditions that are tissue specific. The present study investigated such mechanisms in castrated male rats (75% reduction in testosterone) with demonstrated glucose intolerance. Over 9 wk, castration impaired body weight gain, which resulted from a reduced lean body mass and preferential sparing of adipose tissue. Castration decreased gastrocnemius weight, but this atrophy was not associated with reduced basal muscle protein synthesis or differences in plasma IGF-I, insulin, or individual amino acids. However, oral leucine failed to normally stimulate muscle protein synthesis in castrated rats. In addition, castration-induced atrophy was associated with increased 3-methylhistidine excretion and in vitro-determined ubiquitin proteasome activity in skeletal muscle, changes that were associated with decreased atrogin-1 or MuRF1 mRNA expression. Castration decreased heart and kidney weight without reducing protein synthesis and did not alter either cardiac output or glomerular filtration. In contradistinction, the weight of the retroperitoneal fat depot was increased in castrated rats. This increase was associated with an elevated rate of basal protein synthesis, which was unresponsive to leucine stimulation. Castration also decreased whole body fat oxidation. Castration increased TNFα, IL-1α, IL-6, and NOS2 mRNA in fat but not muscle. In summary, the castration-induced muscle wasting results from an increased muscle protein breakdown and the inability of leucine to stimulate protein synthesis, whereas the expansion of the retroperitoneal fat depot appears mediated in part by an increased basal rate of protein synthesis-associated increased inflammatory cytokine expression.

  13. Castration differentially alters basal and leucine-stimulated tissue protein synthesis in skeletal muscle and adipose tissue

    PubMed Central

    Jiao, Qianning; Pruznak, Anne M.; Huber, Danuta; Vary, Thomas C.

    2009-01-01

    Reduced testosterone as a result of catabolic illness or aging is associated with loss of muscle and increased adiposity. We hypothesized that these changes in body composition occur because of altered rates of protein synthesis under basal and nutrient-stimulated conditions that are tissue specific. The present study investigated such mechanisms in castrated male rats (75% reduction in testosterone) with demonstrated glucose intolerance. Over 9 wk, castration impaired body weight gain, which resulted from a reduced lean body mass and preferential sparing of adipose tissue. Castration decreased gastrocnemius weight, but this atrophy was not associated with reduced basal muscle protein synthesis or differences in plasma IGF-I, insulin, or individual amino acids. However, oral leucine failed to normally stimulate muscle protein synthesis in castrated rats. In addition, castration-induced atrophy was associated with increased 3-methylhistidine excretion and in vitro-determined ubiquitin proteasome activity in skeletal muscle, changes that were associated with decreased atrogin-1 or MuRF1 mRNA expression. Castration decreased heart and kidney weight without reducing protein synthesis and did not alter either cardiac output or glomerular filtration. In contradistinction, the weight of the retroperitoneal fat depot was increased in castrated rats. This increase was associated with an elevated rate of basal protein synthesis, which was unresponsive to leucine stimulation. Castration also decreased whole body fat oxidation. Castration increased TNFα, IL-1α, IL-6, and NOS2 mRNA in fat but not muscle. In summary, the castration-induced muscle wasting results from an increased muscle protein breakdown and the inability of leucine to stimulate protein synthesis, whereas the expansion of the retroperitoneal fat depot appears mediated in part by an increased basal rate of protein synthesis-associated increased inflammatory cytokine expression. PMID:19755668

  14. Early Stress History Alters Serum Insulin-Like Growth Factor-1 and Impairs Muscle Mitochondrial Function in Adult Male Rats.

    PubMed

    Ghosh, S; Banerjee, K K; Vaidya, V A; Kolthur-Seetharam, U

    2016-09-01

    Early-life adversity is associated with an enhanced risk for adult psychopathology. Psychiatric disorders such as depression exhibit comorbidity for metabolic dysfunction, including obesity and diabetes. However, it is poorly understood whether, besides altering anxiety and depression-like behaviour, early stress also evokes dysregulation of metabolic pathways and enhances vulnerability for metabolic disorders. We used the rodent model of the early stress of maternal separation (ES) to examine the effects of early stress on serum metabolites, insulin-like growth factor (IGF)-1 signalling, and muscle mitochondrial content. Adult ES animals exhibited dyslipidaemia, decreased serum IGF1 levels, increased expression of liver IGF binding proteins, and a decline in the expression of specific metabolic genes in the liver and muscle, including Pck1, Lpl, Pdk4 and Hmox1. These changes occurred in the absence of alterations in body weight, food intake, glucose tolerance, insulin tolerance or insulin levels. ES animals also exhibited a decline in markers of muscle mitochondrial content, such as mitochondrial DNA levels and expression of TFAM (transcription factor A, mitochondrial). Furthermore, the expression of several genes involved in mitochondrial function, such as Ppargc1a, Nrf1, Tfam, Cat, Sesn3 and Ucp3, was reduced in skeletal muscle. Adult-onset chronic unpredictable stress resulted in overlapping and distinct consequences from ES, including increased circulating triglyceride levels, and a decline in the expression of specific metabolic genes in the liver and muscle, with no change in the expression of genes involved in muscle mitochondrial function. Taken together, our results indicate that a history of early adversity can evoke persistent changes in circulating IGF-1 and muscle mitochondrial function and content, which could serve to enhance predisposition for metabolic dysfunction in adulthood. © 2016 British Society for Neuroendocrinology.

  15. Reduced Neck Muscle Strength and Altered Muscle Mechanical Properties in Cervical Dystonia Following Botulinum Neurotoxin Injections: A Prospective Study

    PubMed Central

    Mustalampi, Sirpa; Ylinen, Jari; Korniloff, Katariina; Weir, Adam; Häkkinen, Arja

    2016-01-01

    Objective To evaluate changes in the strength and mechanical properties of neck muscles and disability in patients with cervical dystonia (CD) during a 12-week period following botulinum neurotoxin (BoNT) injections. Methods Eight patients with CD volunteered for this prospective clinical cohort study. Patients had received BoNT injections regularly in neck muscles at three-month intervals for several years. Maximal isometric neck strength was measured by a dynamometer, and the mechanical properties of the splenius capitis were evaluated using two myotonometers. Clinical assessment was performed using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) before and at 2, 4, 8, and 12 weeks after the BoNT injections. Results Mean maximal isometric neck strength at two weeks after the BoNT injections decreased by 28% in extension, 25% in rotation of the affected side and 17% in flexion. At four weeks, muscle stiffness of the affected side decreased by 17% and tension decreased by 6%. At eight weeks, the muscle elasticity on the affected side increased by 12%. At two weeks after the BoNT injections, the TWSTRS-severity and TWSTRS-total scores decreased by 4.3 and 6.4, respectively. The strength, muscle mechanical properties and TWSTRS scores returned to baseline values at 12 weeks. Conclusions Although maximal neck strength and muscle tone decreased after BoNT injections, the disability improved. The changes observed after BoNT injections were temporary and returned to pre-injection levels within twelve weeks. Despite having a possible negative effect on function and decreasing neck strength, the BoNT injections improved the patients reported disability. PMID:26828215

  16. Differential cysteine labeling and global label-free proteomics reveals an altered metabolic state in skeletal muscle aging.

    PubMed

    McDonagh, Brian; Sakellariou, Giorgos K; Smith, Neil T; Brownridge, Philip; Jackson, Malcolm J

    2014-11-07

    The molecular mechanisms underlying skeletal muscle aging and associated sarcopenia have been linked to an altered oxidative status of redox-sensitive proteins. Reactive oxygen and reactive nitrogen species (ROS/RNS) generated by contracting skeletal muscle are necessary for optimal protein function, signaling, and adaptation. To investigate the redox proteome of aging gastrocnemius muscles from adult and old male mice, we developed a label-free quantitative proteomic approach that includes a differential cysteine labeling step. The approach allows simultaneous identification of up- and downregulated proteins between samples in addition to the identification and relative quantification of the reversible oxidation state of susceptible redox cysteine residues. Results from muscles of adult and old mice indicate significant changes in the content of chaperone, glucose metabolism, and cytoskeletal regulatory proteins, including Protein DJ-1, cAMP-dependent protein kinase type II, 78 kDa glucose regulated protein, and a reduction in the number of redox-responsive proteins identified in muscle of old mice. Results demonstrate skeletal muscle aging causes a reduction in redox-sensitive proteins involved in the generation of precursor metabolites and energy metabolism, indicating a loss in the flexibility of the redox energy response. Data is available via ProteomeXchange with identifier PXD001054.

  17. Differential Cysteine Labeling and Global Label-Free Proteomics Reveals an Altered Metabolic State in Skeletal Muscle Aging

    PubMed Central

    2014-01-01

    The molecular mechanisms underlying skeletal muscle aging and associated sarcopenia have been linked to an altered oxidative status of redox-sensitive proteins. Reactive oxygen and reactive nitrogen species (ROS/RNS) generated by contracting skeletal muscle are necessary for optimal protein function, signaling, and adaptation. To investigate the redox proteome of aging gastrocnemius muscles from adult and old male mice, we developed a label-free quantitative proteomic approach that includes a differential cysteine labeling step. The approach allows simultaneous identification of up- and downregulated proteins between samples in addition to the identification and relative quantification of the reversible oxidation state of susceptible redox cysteine residues. Results from muscles of adult and old mice indicate significant changes in the content of chaperone, glucose metabolism, and cytoskeletal regulatory proteins, including Protein DJ-1, cAMP-dependent protein kinase type II, 78 kDa glucose regulated protein, and a reduction in the number of redox-responsive proteins identified in muscle of old mice. Results demonstrate skeletal muscle aging causes a reduction in redox-sensitive proteins involved in the generation of precursor metabolites and energy metabolism, indicating a loss in the flexibility of the redox energy response. Data is available via ProteomeXchange with identifier PXD001054. PMID:25181601

  18. High intracellular [Ca2+] alters sarcoplasmic reticulum function in skinned skeletal muscle fibres of the rat

    PubMed Central

    Lamb, G D; Cellini, M A

    1999-01-01

    The effect on sarcoplasmic reticulum (SR) function of exposure to high intracellular [Ca2+] was studied in mechanically skinned fibres from the extensor digitorum longus muscle of the rat, using caffeine to assay the SR Ca2+ content. A 15 s exposure to 50 μm Ca2+ irreversibly reduced the ability of the SR to load/retain Ca2+ and completely abolished depolarization-induced Ca2+ release, whereas a 90 s exposure to 10 μm Ca2+ had no detectable effect on either function. The reduction in net SR Ca2+ uptake: (a) was near-maximal with treatment at 50 μm Ca2+, (b) was unrelated to voltage-sensor function, and (c) persisted unchanged for > 20 min. The reduction was primarily due to a threefold increase in leakage of Ca2+ out of the SR. This increased leakage was not substantially blocked by the presence of 10 mM Mg2+ or 2 μm Ruthenium Red. The adverse effect on SR function of exposure to high [Ca2+] could also be observed by the reduction in the ability of the SR to maintain a low [Ca2+] within the skinned fibre in the face of elevated [Ca2+] in the bathing solution. When bathed in a solution with ≈1.5 μm Ca2+ (0.75 mM CaEGTA-EGTA), skinned fibres produced only low force responses for many minutes, but after high [Ca2+] treatment (15 s exposure to 50 μm Ca2+) they showed large, steady or oscillatory force responses. These findings indicate that, in addition to uncoupling the Ca2+ release channels from the voltage sensors, exposure of skinned fibres to high [Ca2+] causes a persistent increase in resting Ca2+ efflux from the SR. Such efflux in an intact fibre would alter the distribution of Ca2+ between the SR, the cytoplasm and the extracellular solution. These results may be relevant to the basis of low-frequency fatigue and possibly other conditions in muscle. PMID:10457093

  19. Altered Splicing of the BIN1 Muscle-Specific Exon in Humans and Dogs with Highly Progressive Centronuclear Myopathy

    PubMed Central

    Böhm, Johann; Vasli, Nasim; Maurer, Marie; Cowling, Belinda; Shelton, G. Diane; Kress, Wolfram; Toussaint, Anne; Prokic, Ivana; Schara, Ulrike; Anderson, Thomas James; Weis, Joachim; Tiret, Laurent; Laporte, Jocelyn

    2013-01-01

    Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies. PMID:23754947

  20. Morphomechanical alterations in the medial gastrocnemius muscle in patients with a repaired Achilles tendon: Associations with outcome measures.

    PubMed

    Peng, Wei-Chen; Chang, Yi-Ping; Chao, Yuan-Hung; Fu, S N; Rolf, Christer; Shih, Tiffany Tf; Su, Sheng-Chu; Wang, Hsing-Kuo

    2017-03-01

    Functional deficits are found in ankles that have sustained an Achilles rupture. This study sought to evaluate and compare the morphomechanical characteristics of the medial gastrocnemius muscle in the legs of participants within six months of a unilateral Achilles repair to determine any correlations between those characteristics and objective outcomes and self-reported functional levels. Fifteen participants were assessed via measurements of muscle morphologies (fascicle length, pennation angle, and muscle thickness) in a resting state, the mechanical properties of the proximal aponeurosis of the medial gastrocnemius muscle, the pennation angle during ramping maximal voluntary isometric contractions (MVIC), the heel raise test, and the Taiwan Chinese version of the Lower Extremity Functional Scale (LEFS-TC) questionnaire. Findings Compared with the non-injured legs, the repaired legs showed a lower muscle fascicle length (mean 4.4 vs. 5.0cm) and thickness (1.7 vs. 1.9cm), lower stiffness of the GM tendon and aponeurosis (174.1 vs. 375.6N/mm), and a greater GM pennation angle (31.2 vs. 28.9°) during 90% MVIC (all p≤0.05). Correlations were found between the morphomechanical results and maximal heel raise heights or the LEFS-TC score, and between the symmetry ratios of the fascicle lengths and the LEFS-TC score. Interpretation There are decreases in fascicle length, muscle thickness and mechanical properties in the medial gastrocnemius muscles of the participants within the first six months after an Achilles repair. These morphomechanical alterations demonstrate associations with functional levels in the lower extremities and indicated the need for early mobilization of the calf muscles after the repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Novel roles of FKBP5 in muscle alteration induced by gravity change in mice.

    PubMed

    Shimoide, Takeshi; Kawao, Naoyuki; Tamura, Yukinori; Morita, Hironobu; Kaji, Hiroshi

    2016-10-21

    Skeletal muscle hypertrophy and wasting are induced by hypergravity and microgravity, respectively. However, the mechanisms by which gravity change regulates muscle mass still remain unclear. We previously reported that hypergravity increases muscle mass via the vestibular system in mice. In this study, we performed comparative DNA microarray analysis of the soleus muscle from mice kept in 1 or 3 g environments with or without vestibular lesions. Mice were kept in 1 g or 3 g environment for 4 weeks by using a centrifuge 14 days after surgical bilateral vestibular lesions. FKBP5 was extracted as a gene whose expression was enhanced by hypergravity through the vestibular system. Stable FKBP5 overexpression increased the phosphorylations of Akt and p70 S6 kinase (muscle protein synthesis pathway) and myosin heavy chain, a myotube gene, mRNA level in mouse myoblastic C2C12 cells, although it reduced the mRNA levels of atrogin-1 and MuRF1, muscle protein degradation-related genes. In conclusion, we first showed that FKBP5 is induced by hypergravity through the vestibular system in anti-gravity muscle of mice. Our data suggest that FKBP5 might increase muscle mass through the enhancements of muscle protein synthesis and myotube differentiation as well as an inhibition of muscle protein degradation in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Collagen synthesis by cultured rabbit aortic smooth-muscle cells. Alteration with phenotype.

    PubMed Central

    Ang, A H; Tachas, G; Campbell, J H; Bateman, J F; Campbell, G R

    1990-01-01

    Enzymically isolated rabbit aortic smooth-muscle cells (SMC) in the first few days of primary culture express a 'contractile phenotype', but with time these cells modulate to a 'synthetic phenotype'. Synthetic-state SMC are able to proliferate, and, provided that they undergo fewer than 5 cumulative population doublings, return to the contractile phenotype after reaching confluency [Campbell, Kocher, Skalli, Gabbiani & Campbell (1989) Arteriosclerosis 9, 633-643]. The present study has determined the synthesis of collagen, at the protein and mRNA levels, by cultured SMC as they undergo a change in phenotypic state. The results show that, upon modulating to the synthetic phenotype, SMC synthesized 25-30 times more collagen than did contractile cells. At the same time, non-collagen-protein synthesis increased only 5-6-fold, indicating a specific stimulation of collagen synthesis. Steady-state mRNA levels are also elevated, with alpha 2(I) and alpha 1(III) mRNA levels 30 times and 20 times higher respectively, probably reflecting increased transcriptional activity. Phenotypic modulation was also associated with an alteration in the relative proportions of type I and III collagens synthesized, contractile SMC synthesizing 78.1 +/- 3.6% (mean +/- S.D.) type I collagen and 17.5 +/- 4.7% type III collagen, and synthetic cells synthesizing 90.3 +/- 2.0% type I collagen and 5.8% +/- 1.8% type III collagen. Enrichment of type I collagen was similarly noted at the mRNA level. On return to the contractile state, at confluency, collagen production and the percentage of type I collagen decreased. This further illustrates the close association between the phenotypic state of SMC and their collagen-biosynthetic phenotype. Images Fig. 4. PMID:1689147

  3. HANAC Col4a1 Mutation in Mice Leads to Skeletal Muscle Alterations due to a Primary Vascular Defect.

    PubMed

    Guiraud, Simon; Migeon, Tiffany; Ferry, Arnaud; Chen, Zhiyong; Ouchelouche, Souhila; Verpont, Marie-Christine; Sado, Yoshikazu; Allamand, Valérie; Ronco, Pierre; Plaisier, Emmanuelle

    2017-03-01

    Collagen IV is a major component of basement membranes (BMs). The α1(IV) chain, encoded by the COL4A1 gene, is expressed ubiquitously and associates with the α2(IV) chain to form the α1α1α2(IV) heterotrimer. Several COL4A1 mutations affecting a conformational domain containing integrin-binding sites are responsible for the systemic syndrome of hereditary angiopathy, nephropathy, aneurysms, and cramps (HANAC). To analyze the pathophysiology of HANAC, Col4a1 mutant mice bearing the p.Gly498Val mutation were generated. Analysis of the skeletal muscles of Col4a1(G498V) mutant animals showed morphologic characteristics of a muscular dystrophy phenotype with myofiber atrophy, centronucleation, focal inflammatory infiltrates, and fibrosis. Abnormal ultrastructural aspects of muscle BMs was associated with reduced extracellular secretion of the mutant α1α1α2(IV) trimer. In addition to muscular dystrophic features, endothelial cell defects of the muscle capillaries were observed, with intracytoplasmic accumulation of the mutant α1α1α2(IV) molecules, endoplasmic reticulum cisternae dilation, and up-regulation of endoplasmic reticulum stress markers. Induction of the unfolded protein response in Col4a1 mutant muscle tissue resulted in an excess of apoptosis in endothelial cells. HANAC mutant animals also presented with a muscular functional impairment and increased serum creatine kinase levels reflecting altered muscle fiber sarcolemma. This extensive description of the muscular phenotype of the Col4a1 HANAC murine model suggests a potential contribution of primary endothelial cell defects, together with muscle BM alterations, to the development of COL4A1-related myopathy.

  4. Does long-term passive stretching alter muscle-tendon unit mechanics in children with spastic cerebral palsy?

    PubMed

    Theis, Nicola; Korff, Thomas; Mohagheghi, Amir A

    2015-12-01

    Cerebral palsy causes motor impairments during development and many children may experience excessive neural and mechanical muscle stiffness. The clinical assumption is that excessive stiffness is thought to be one of the main reasons for functional impairments in cerebral palsy. As such, passive stretching is widely used to reduce stiffness, with a view to improving function. However, current research evidence on passive stretching in cerebral palsy is not adequate to support or refute the effectiveness of stretching as a management strategy to reduce stiffness and/or improve function. The purpose was to identify the effect of six weeks passive ankle stretching on muscle-tendon unit parameters in children with spastic cerebral palsy. Thirteen children (8-14 y) with quadriplegic/diplegic cerebral palsy were randomly assigned to either an experimental group (n=7) or a control group (n=6). The experimental group underwent an additional six weeks of passive ankle dorsiflexion stretching for 15 min (per leg), four days per week, whilst the control group continued with their normal routine, which was similar for the two groups. Measures of muscle and tendon stiffness, strain and resting length were acquired pre- and post-intervention. The experimental group demonstrated a 3° increase in maximum ankle dorsiflexion. This was accompanied by a 13% reduction in triceps surae muscle stiffness, with no change in tendon stiffness. Additionally, there was an increase in fascicle strain with no changes in resting length, suggesting muscle stiffness reductions were a result of alterations in intra/extra-muscular connective tissue. The results demonstrate that stretching can reduce muscle stiffness by altering fascicle strain but not resting fascicle length. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca2+ buffering protein parvalbumin.

    PubMed

    Chin, Eva R; Grange, Robert W; Viau, Francois; Simard, Alain R; Humphries, Caroline; Shelton, John; Bassel-Duby, Rhonda; Williams, R Sanders; Michel, Robin N

    2003-03-01

    The purpose of this study was to determine whether induced expression of the Ca2+ buffering protein parvalbumin (PV) in slow-twitch fibres would lead to alterations in physiological, biochemical and molecular properties reflective of a fast fibre phenotype. Transgenic (TG) mice were generated that overexpressed PV in slow (type I) muscle fibres. In soleus muscle (SOL; 58 % type I fibres) total PV expression was 2- to 6-fold higher in TG compared to wild-type (WT) mice. Maximum twitch and tetanic tensions were similar in WT and TG but force at subtetanic frequencies (30 and 50 Hz) was reduced in TG SOL. Twitch time-to-peak tension and half-relaxation time were significantly decreased in TG SOL (time-to-peak tension: 39.3 +/- 2.6 vs. 55.1 +/- 4.7 ms; half-relaxation time: 42.1 +/- 3.5 vs. 68.1 +/- 9.6 ms, P < 0.05 for TG vs. WT, respectively; n = 8-10). There was a significant increase in expression of type IIa myosin heavy chain (MHC) and ryanodine receptor at the mRNA level in TG SOL but there were no differences in MHC expression at the protein level and thus no difference in fibre type. Whole muscle succinate dehydrogenase activity was reduced by 12 +/- 0.4 % in TG SOL and single fibre glycerol-3-phosphate dehydrogenase activity was decreased in a subset of type IIa fibres. These differences were associated with a 64 % reduction in calcineurin activity in TG SOL. These data show that overexpression of PV, resulting in decreased calcineurin activity, can alter the functional and metabolic profile of muscle and influence the expression of key marker genes in a predominantly slow-twitch muscle with minimal effects on the expression of muscle contractile proteins.

  6. Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration

    PubMed Central

    Gifford, Jayson R.; Trinity, Joel D.; Layec, Gwenael; Garten, Ryan S.; Park, Song-Young; Rossman, Matthew J.; Larsen, Steen; Dela, Flemming

    2015-01-01

    This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex II (CII)-driven State 3 mitochondrial respiration were measured separately (State 3:CI and State 3:CII) and in combination (State 3:CI+CII). State 2 respiration was also measured. Exercise tolerance was assessed by knee extensor exercise (KE) time to fatigue. Per milligram of muscle, State 3:CI+CII and State 3:CI were reduced in COPD (P < 0.05), while State 3:CII and State 2 were not different between groups. To determine if this altered pattern of respiration represented qualitative changes in mitochondrial function, respiration states were examined as percentages of peak respiration (State 3:CI+CII), which revealed altered contributions from State 3:CI (Con 83.7 ± 3.4, COPD 72.1 ± 2.4%Peak, P < 0.05) and State 3:CII (Con 64.9 ± 3.2, COPD 79.5 ± 3.0%Peak, P < 0.05) respiration, but not State 2 respiration in COPD. Importantly, a diminished contribution of CI-driven respiration relative to the metabolically less-efficient CII-driven respiration (CI/CII) was also observed in COPD (Con 1.28 ± 0.09, COPD 0.81 ± 0.05, P < 0.05), which was related to exercise tolerance of the patients (r = 0.64, P < 0.05). Overall, this study indicates that COPD is associated with qualitative alterations in skeletal muscle mitochondria that affect the contribution of CI and CII-driven respiration, which potentially contributes to the exercise intolerance associated with this disease. PMID:26272320

  7. Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration.

    PubMed

    Gifford, Jayson R; Trinity, Joel D; Layec, Gwenael; Garten, Ryan S; Park, Song-Young; Rossman, Matthew J; Larsen, Steen; Dela, Flemming; Richardson, Russell S

    2015-10-15

    This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex II (CII)-driven State 3 mitochondrial respiration were measured separately (State 3:CI and State 3:CII) and in combination (State 3:CI+CII). State 2 respiration was also measured. Exercise tolerance was assessed by knee extensor exercise (KE) time to fatigue. Per milligram of muscle, State 3:CI+CII and State 3:CI were reduced in COPD (P < 0.05), while State 3:CII and State 2 were not different between groups. To determine if this altered pattern of respiration represented qualitative changes in mitochondrial function, respiration states were examined as percentages of peak respiration (State 3:CI+CII), which revealed altered contributions from State 3:CI (Con 83.7 ± 3.4, COPD 72.1 ± 2.4%Peak, P < 0.05) and State 3:CII (Con 64.9 ± 3.2, COPD 79.5 ± 3.0%Peak, P < 0.05) respiration, but not State 2 respiration in COPD. Importantly, a diminished contribution of CI-driven respiration relative to the metabolically less-efficient CII-driven respiration (CI/CII) was also observed in COPD (Con 1.28 ± 0.09, COPD 0.81 ± 0.05, P < 0.05), which was related to exercise tolerance of the patients (r = 0.64, P < 0.05). Overall, this study indicates that COPD is associated with qualitative alterations in skeletal muscle mitochondria that affect the contribution of CI and CII-driven respiration, which potentially contributes to the exercise intolerance associated with this disease.

  8. Synergistic ablation does not affect atrophy or altered myosin heavy chain expression in the non-weight bearing soleus muscle

    NASA Technical Reports Server (NTRS)

    Linderman, J. K.; Talmadge, R. J.; Gosselink, K. L.; Tri, P. N.; Roy, R. R.; Grindeland, R. E.

    1996-01-01

    The purpose of this study was to investigate whether the soleus muscle undergoes atrophy and alterations in myosin heavy chain (MHC) composition during non-weight bearing in the absence of synergists. Thirty-two female rats were randomly assigned to four groups: control (C), synergistic ablation (ABL) of the gastrocnemius and plantaris muscles to overload the soleus muscle, hindlimb suspension (HLS), or a combination of synergistic ablation and hindlimb suspension (HLS-ABL). After 28 days of hindlimb suspension, soleus atrophy was more pronounced in HLS (58%) than in HLS-ABL (43%) rats. Compared to C rats, non-weight bearing decreased mixed and myofibrillar protein contents and Type I MHC 49%, 45%, and 7%, respectively, in HLS animals. In addition, de novo expression of fast Type IIx and Type IIb MHC (5% and 2%, respectively) was observed in HLS animals. Similarly, when compared to C rats, mixed and myofibrillar protein contents and Type I MHC decreased 43%, 46%, and 4%, respectively, in HLS-ABL animals. Also, de novo expression of Type IIx (4%) and IIb (1%) MHC was observed. Collectively, these data indicate that the loss of muscle protein and Type I MHC, and the de novo expression of Type IIx and Type IIb MHC in the rat soleus occur independently of the presence of synergists during non-weight bearing. Furthermore, these results confirm the contention that soleus mass and MHC expression are highly sensitive to alterations in mechanical load.

  9. Exercise and suspension hypokinesia-induced alterations in mechanical properties of rat fast and slow-twitch skeletal muscles.

    PubMed

    Ertunc, M; Atalay, A; Yildirim, M; Onur, R

    2010-09-01

    Physical activity has a modulatory role on regulatory steps of excitation-contraction coupling (ECC) determining skeletal muscle contractility. We evaluated and compared the contractile responsiveness and caffeine-induced contractures of fast (extensor digitorum longus; EDL) and slow-twitch (soleus; SOL) muscles in suspension hypokinesia (SH) and exercised rats. After SH or low intensity exercise, EDL and SOL were isolated, twitch and tetanic contractions and caffeine (10 mM) contractures were recorded. Twitch and tetanic contractions of EDL increased by 60% in exercised rats (p <0.05) while no alteration was observed after SH. Exercise did not alter twitch and tetanic contractions of SOL, while SH depressed contractions (p <0.05). Caffeine contractures were diminished in exercised rat EDL (P <0.05). In SH-rat EDL, contractures increased in amplitude (p <0.01) with a rapid time course (p <0.05). Contractures did not change in SOL after exercise or SH. We concluded that SH and exercise exerted diverse modulatory effects on skeletal muscle contractility. Contractile improvement due to exercise was prominent in EDL. Our results suggest that the muscle-type specific adaptations are related to a change in ECC due to the differences in the regulatory steps, particularly in the intracellular Ca(2+) handling mechanisms.

  10. Synergistic ablation does not affect atrophy or altered myosin heavy chain expression in the non-weight bearing soleus muscle

    NASA Technical Reports Server (NTRS)

    Linderman, J. K.; Talmadge, R. J.; Gosselink, K. L.; Tri, P. N.; Roy, R. R.; Grindeland, R. E.

    1996-01-01

    The purpose of this study was to investigate whether the soleus muscle undergoes atrophy and alterations in myosin heavy chain (MHC) composition during non-weight bearing in the absence of synergists. Thirty-two female rats were randomly assigned to four groups: control (C), synergistic ablation (ABL) of the gastrocnemius and plantaris muscles to overload the soleus muscle, hindlimb suspension (HLS), or a combination of synergistic ablation and hindlimb suspension (HLS-ABL). After 28 days of hindlimb suspension, soleus atrophy was more pronounced in HLS (58%) than in HLS-ABL (43%) rats. Compared to C rats, non-weight bearing decreased mixed and myofibrillar protein contents and Type I MHC 49%, 45%, and 7%, respectively, in HLS animals. In addition, de novo expression of fast Type IIx and Type IIb MHC (5% and 2%, respectively) was observed in HLS animals. Similarly, when compared to C rats, mixed and myofibrillar protein contents and Type I MHC decreased 43%, 46%, and 4%, respectively, in HLS-ABL animals. Also, de novo expression of Type IIx (4%) and IIb (1%) MHC was observed. Collectively, these data indicate that the loss of muscle protein and Type I MHC, and the de novo expression of Type IIx and Type IIb MHC in the rat soleus occur independently of the presence of synergists during non-weight bearing. Furthermore, these results confirm the contention that soleus mass and MHC expression are highly sensitive to alterations in mechanical load.

  11. Major alteration of the pathological phenotype in gamma irradiated mdx soleus muscles

    SciTech Connect

    Weller, B.; Karpati, G.; Lehnert, S.; Carpenter, S. )

    1991-07-01

    Two thousand rads of gamma irradiation delivered to the lower legs of ten day old normal and x-chromosome linked muscular dystrophy (mdx) mice caused significant inhibition of tibial bone and soleus muscle fiber growth. In the irradiated mdx solei, there was a major loss of muscle fibers, lack of central nucleation, and some endomysial fibrosis. These features were caused by a failure of regeneration of muscle fibers due to impaired proliferative capacity of satellite cells. Gamma irradiation transforms the late pathological phenotype of mdx muscles, so that in one major aspect (muscle fiber loss) they resemble muscles in Duchenne muscular dystrophy. However, extensive endomysial fibrosis which is another characteristic feature of Duchenne muscular dystrophy did not develop. This experimental model could be useful for the functional investigation of possible beneficial effects of therapeutic interventions in mdx dystrophy.

  12. Counting carbohydrates

    MedlinePlus

    ... There are 3 major types of carbohydrates: Sugars Starches Fiber Sugars are found naturally in some foods ... syrups, such as those added to canned fruit Starches are found naturally in foods. Your body breaks ...

  13. Effect of taurine supplementation on the alterations in amino Acid content in skeletal muscle with exercise in rat.

    PubMed

    Ishikura, Keisuke; Miyazaki, Teruo; Ra, Song-Gyu; Endo, Shoji; Nakamura, Yusuke; Matsuzaka, Takashi; Miyakawa, Shumpei; Ohmori, Hajime

    2011-01-01

    precursor for gluconeogenesis.The alteration of three amino acids in muscles was maintained after exhausted exercise.The muscular alterations of them might be one of taurine-induced roles on exercise performance.

  14. Effect of Taurine Supplementation on the Alterations in Amino Acid Content in Skeletal Muscle with Exercise in Rat

    PubMed Central

    Ishikura, Keisuke; Miyazaki, Teruo; Ra, Song-Gyu; Endo, Shoji; Nakamura, Yusuke; Matsuzaka, Takashi; Miyakawa, Shumpei; Ohmori, Hajime

    2011-01-01

    precursor for gluconeogenesis. The alteration of three amino acids in muscles was maintained after exhausted exercise. The muscular alterations of them might be one of taurine-induced roles on exercise performance. PMID:24149876

  15. γ-Rays-generated ROS induce apoptosis via mitochondrial and cell cycle alteration in smooth muscle cells.

    PubMed

    Claro, Sandra; Oshiro, Maria Etsuko Miyamoto; Mortara, Renato Arruda; Paredes-Gamero, Edgar Julian; Pereira, Gustavo José Silva; Smaili, Soraya Soubhi; Ferreira, Alice Teixeira

    2014-10-01

    γ-rays (IR) cause an increase in intracellular calcium [Ca(2+)], alters contractility and triggers apoptosis via the activation of protein kinase C in intestinal guinea pig smooth muscle cells. The present study investigated the role of the mitochondria in these processes and characterized proteins involved in IR-induced apoptosis. Intestinal smooth muscle cells were exposed to 10-50 Gy from a (60)Co γ-source. Reactive oxygen species (ROS) levels were measured by colourimetry with a fluorescente probe. Protein expression was analyzed by immunoblotting and immunofluorescence. Apoptosis was inhibited by glutathione, possible by inhibiting the generation or scavenging ROS. Apoptosis was mediated by the mitochondria releasing cytochrome c leading to caspase 3 activation. IR increased the expression of the cyclins A, B2 and E and led to unbalanced cellular growth in an absorption dose-dependent manner. However, radiation did not induce alterations in the mitochondrial ultrastructure or in transmembrane electric potential. In contrast, IR increased the nuclear expression of cytoplasmic proteins and cyclins A and E. Smooth muscle cells subjected to IR undergo mitochondrial-mediated apoptosis that involves oncoproteins activation and preserves mitochondrial structure. IR also cause alterations in the expression and localization of both pro- and anti-apoptotic proteins.

  16. Short-term recovery from prolonged exercise: exploring the potential for protein ingestion to accentuate the benefits of carbohydrate supplements.

    PubMed

    Betts, James A; Williams, Clyde

    2010-11-01

    This review considers aspects of the optimal nutritional strategy for recovery from prolonged moderate to high intensity exercise. Dietary carbohydrate represents a central component of post-exercise nutrition. Therefore, carbohydrate should be ingested as early as possible in the post-exercise period and at frequent (i.e. 15- to 30-minute) intervals throughout recovery to maximize the rate of muscle glycogen resynthesis. Solid and liquid carbohydrate supplements or whole foods can achieve this aim with equal effect but should be of high glycaemic index and ingested following the feeding schedule described above at a rate of at least 1 g/kg/h in order to rapidly and sufficiently increase both blood glucose and insulin concentrations throughout recovery. Adding ≥0.3 g/kg/h of protein to a carbohydrate supplement results in a synergistic increase in insulin secretion that can, in some circumstances, accelerate muscle glycogen resynthesis. Specifically, if carbohydrate has not been ingested in quantities sufficient to maximize the rate of muscle glycogen resynthesis, the inclusion of protein may at least partially compensate for the limited availability of ingested carbohydrate. Some studies have reported improved physical performance with ingestion of carbohydrate-protein mixtures, both during exercise and during recovery prior to a subsequent exercise test. While not all of the evidence supports these ergogenic benefits, there is clearly the potential for improved performance under certain conditions, e.g. if the additional protein increases the energy content of a supplement and/or the carbohydrate fraction is ingested at below the recommended rate. The underlying mechanism for such effects may be partly due to increased muscle glycogen resynthesis during recovery, although there is varied support for other factors such as an increased central drive to exercise, a blunting of exercise-induced muscle damage, altered metabolism during exercise subsequent to

  17. Lumbar muscle inflammation alters spinally mediated locomotor recovery induced by training in a mouse model of complete spinal cord injury.

    PubMed

    Jeffrey-Gauthier, Renaud; Piché, Mathieu; Leblond, Hugues

    2017-09-17

    Locomotor networks after spinal cord injury (SCI) are shaped by training-activated proprioceptive and cutaneous inputs. Nociception from injured tissues may alter these changes but has largely been overlooked. The objective of the present study was to ascertain whether lumbar muscle inflammation hinders locomotion recovery in a mouse model of complete SCI. Lower limb kinematics during treadmill training was assessed before and after complete SCI at T8 (2, 7, 14, 21 and 28days post-injury). Locomotor recovery was compared in 4 groups of CD1 mice: control spinal mice; spinal mice with daily locomotor training; spinal mice with lumbar muscle inflammation (Complete Freund's Adjuvant (CFA) injection); and spinal mice with locomotor training and CFA. On day 28, H-reflex excitability and its inhibition at high-frequency stimulation (frequency-dependent depression: FDD) were compared between groups, all of which showed locomotor recovery. Recovery was enhanced by training, whereas lumbar muscle inflammation hindered these effects (knee angular excursion and paw drag: p's<0.05). In addition, lumbar muscle inflammation impaired hind limb coupling during locomotion (p<0.05) throughout recovery. Also, H-reflex disinhibition was prevented by training, with or without CFA injection (p's<0.05). Altogether, these results indicate that back muscle inflammation modulates spinally mediated locomotor recovery in mice with complete SCI, in part, by reducing adaptive changes induced by training. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  18. Changes in photoperiod alter Glut4 expression in skeletal muscle of C57BL/6J mice.

    PubMed

    Tashiro, Ayako; Shibata, Satomi; Takai, Yusuke; Uchiwa, Tatsuhiro; Furuse, Mitsuhiro; Yasuo, Shinobu

    2017-03-25

    Seasonal changes in photoperiod influence body weight and metabolism in mice. Here, we examined the effect of changes in photoperiod on the expression of glucose transporter genes in the skeletal muscle and adipose tissue of C57BL/6J mice. Glut4 expression was lower in the gastrocnemius muscle of mice exposed to a short-duration day (SD) than those to a long-duration day (LD), with accompanying changes in GLUT4 protein levels. Although Glut4 expression in the mouse soleus muscle was higher under SD than under LD, GLUT4 protein levels remained unchanged. To confirm the functional significance of photoperiod-induced changes in Glut4 expression, we checked for variations in insulin sensitivity. Blood glucose levels after insulin injection remained high under SD, suggesting that the mice exposed to SD showed lower sensitivity to insulin than those exposed to LD. We also attempted to clarify the relationship between Glut4 expression and physical activity in the mice following changes in photoperiod. Locomotor activity, as detected via infrared beam sensor, was lower under SD than under LD. However, when we facilitated voluntary activity by using running wheels, the rotation of wheels was similar for both groups of mice. Although physical activity levels were enhanced due to running wheels, Glut4 expression in the gastrocnemius muscle remained unchanged. Thus, variations in photoperiod altered Glut4 expression in the mouse skeletal muscle, with subsequent changes in GLUT4 protein levels and insulin sensitivity; these effects might be independent of physical activity.

  19. Peanut protein reduces body protein mass and alters skeletal muscle contractile properties and lipid metabolism in rats.

    PubMed

    Jacques, Hélène; Leblanc, Nadine; Papineau, Roxanne; Richard, Denis; Côté, Claude H

    2010-05-01

    It is well known that diets high in nuts or peanuts favourably affect plasma lipid concentrations. However, few studies have examined the effects of nut and peanut protein (PP) on body composition and skeletal muscle properties. The present study was aimed at evaluating the effect of dietary PP compared with two animal proteins, casein (C) and cod protein (CP) on body composition, skeletal muscle contractile properties and lipid metabolism in rats. Thirty-two male rats were assigned to one of the following four diets containing either C, CP, PP or C+peanut protein (CPP, 50:50) mixture. After 28 d of ad libitum feeding and after 12-h fast, blood, liver and muscle were collected for measurements of plasma and hepatic cholesterol and TAG, plasma glucose and insulin and contractile properties. Rats fed with the low-quality protein, PP, had lower body weight gain, body protein mass, soleus mass and liver weight than those fed with the high-quality dietary proteins, C and CP. PP also caused a deficit in contractile properties in soleus. Likewise, PP increased plasma cholesterol and body fat mass compared with CP. However, these elevations were accompanied with increased hepatic TAG concentrations and lowered intestinal fat excretion. These results show that PP intake alters body composition by reducing skeletal muscle mass and liver weight as well as muscle contractility and lipid metabolism. Adding a complete protein such as C might partially counteract these adverse effects.

  20. Late-onset caloric restriction alters skeletal muscle metabolism by modulating pyruvate metabolism.

    PubMed

    Chen, Chiao-Nan Joyce; Lin, Shang-Ying; Liao, Yi-Hung; Li, Zhen-Jie; Wong, Alice May-Kuen

    2015-06-01

    Caloric restriction (CR) attenuates age-related muscle loss. However, the underlying mechanism responsible for this attenuation is not fully understood. This study evaluated the role of energy metabolism in the CR-induced attenuation of muscle loss. The aims of this study were twofold: 1) to evaluate the effect of CR on energy metabolism and determine its relationship with muscle mass, and 2) to determine whether the effects of CR are age dependent. Young and middle-aged rats were randomized into either 40% CR or ad libitum (AL) diet groups for 14 wk. Major energy-producing pathways in muscles, i.e., glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), were examined. We found that the effects of CR were age dependent. CR improved muscle metabolism and normalized muscle mass in middle-aged animals but not young animals. CR decreased glycolysis and increased the cellular dependency for OXPHOS vs. glycolysis in muscles of middle-aged rats, which was associated with the improvement of normalized muscle mass. The metabolic reprogramming induced by CR was related to modulation of pyruvate metabolism and increased mitochondrial biogenesis. Compared with animals fed AL, middle-aged animals with CR had lower lactate dehydrogenase A content and greater mitochondrial pyruvate carrier content. Markers of mitochondrial biogenesis, including AMPK activation levels and SIRT1 and COX-IV content, also showed increased levels. In conclusion, 14 wk of CR improved muscle metabolism and preserved muscle mass in middle-aged animals but not in young developing animals. CR-attenuated age-related muscle loss is associated with reprogramming of the metabolic pathway from glycolysis to OXPHOS.

  1. Alteration of the levels of the M-type 6-phosphofructo-1-kinase mRNA isoforms during neonatal maturation of heart, brain and muscle.

    PubMed

    Mhaskar, Y; Armour, G; Dunaway, G

    2000-11-01

    During muscle, heart, and brain neonatal maturation, the capacity to utilize glucose in energy metabolism is directly related to the extent of accumulation of the 6-phosphofructo-1-kinase (PFK) M-type subunit. Neonatal development of other organs, such as liver and kidney, which are not characterized by large increases in the capacity to use glucose do not exhibit large increases in the M-type subunit protein. The presence of the M-type subunit in a PFK isozyme pool fosters a higher affinity utilization of carbohydrate and increased responsiveness to the levels of regulatory metabolites. To better appreciate this phenomenon, which is vital for normal development, the different isoforms of the M-type subunit mRNA's and alteration of their levels during maturation have been examined. Further, the potential promoter regions, i.e., the regions upstream from the sites of initiation of transcription, which are involved in expression of the different M-type subunit mRNA isoforms have been isolated, sequenced, and examined for possible transcription factor interaction sites. Using cDNA libraries produced from adult rat brain or skeletal muscle RNA, two primary forms of rat M-type subunit cDNA's were detected. Although the translated regions of these mRNA's were essentially identical, the 5'-untranslated region (5'-UTR) exhibited different lengths (90 or 59 bp) and sequences. Each M-type subunit cDNA had 10 common nucleotides immediately upstream from the initiator ATG, and the remaining 5'-UTR's had insignificant identity. A genomic fragment which interacted with probes complimentary to the sequences of the 5'-UTR of each M-type subunit mRNA isoform was isolated and sequenced by primer walking. It was discovered that the 5'-UTR of one of the mRNA's (proximal mRNA) was located immediately upstream from exon I and was apparently transcribed without splicing. Subsequently, the initial bp in the sequence of the other mRNA isoform (distal mRNA) was located 4010 bp upstream from

  2. Temporal patterns of the trunk muscles remain altered in a low back-injured population despite subjective reports of recovery.

    PubMed

    Moreside, Janice M; Quirk, D Adam; Hubley-Kozey, Cheryl L

    2014-04-01

    To compare temporal activation patterns from 24 abdominal and lumbar muscles between healthy subjects and those who reported recovery from recent low back injury (LBI). Cross-sectional comparative study. University neuromuscular function laboratory. Healthy adult volunteers (N=81; 30 LBI, 51 asymptomatic subjects). Trunk muscle electromyographic activity was collected during 2 difficulty levels of a supine trunk stability test aimed at challenging lumbopelvic control. Principal component (PC) analysis was applied to determine differences in temporal and/or amplitude electromyographic patterns between groups. Mixed-model analyses of variance were performed on PC scores that explained more than 89% of the variance (α=.05). Four PCs explained 89% and 96% of the variance for the abdominal and back muscles, respectively, with both muscle groups having similar shapes in the first 3 PCs. Significant interactions or group main effects were found for all PC scores except PC4 for the back extensors. Overall activation amplitudes for both the abdominal and back muscles (PC1 scores) were significantly (P<.05) higher for the LBI group, with both abdominal and back muscles of the LBI group demonstrating an increased response to the leg-loading phase (PC2 scores) compared with the asymptomatic group. Differences were also found between groups in their preparatory activity (PC3 scores), with the LBI group having a higher early relative amplitude of abdominal and back extensor activity. Despite perceived readiness to return to work and low pain scores, muscle activation patterns remained altered in this LBI group, including reduced synergistic coactivation and increased overall amplitudes as well as greater relative amplitude differences during specific phases of the movement. Electromyographic measures provide objective information to help guide therapy and may assist with determining the level of healing and return-to-work readiness after an LBI. Copyright © 2014 American

  3. Alterations in multidimensional motor unit number index of hand muscles after incomplete cervical spinal cord injury

    PubMed Central

    Li, Le; Li, Xiaoyan; Liu, Jie; Zhou, Ping

    2015-01-01

    The objective of this study was to apply a novel multidimensional motor unit number index (MD-MUNIX) technique to examine hand muscles in patients with incomplete cervical spinal cord injury (SCI). The MD-MUNIX was estimated from the compound muscle action potential (CMAP) and different levels of surface interference pattern electromyogram (EMG) at multiple directions of voluntary isometric muscle contraction. The MD-MUNIX was applied in the first dorsal interosseous (FDI), thenar and hypothenar muscles of SCI (n = 12) and healthy control (n = 12) subjects. The results showed that the SCI subjects had significantly smaller CMAP and MD-MUNIX in all the three examined muscles, compared to those derived from the healthy control subjects. The multidimensional motor unit size index (MD-MUSIX) demonstrated significantly larger values for the FDI and hypothenar muscles in SCI subjects than those from healthy control subjects, whereas the MD-MUSIX enlargement was marginally significant for the thenar muscles. The findings from the MD-MUNIX analyses provide an evidence of motor unit loss in hand muscles of cervical SCI patients, contributing to hand function deterioration. PMID:26005410

  4. Effect of timing of surgical SSP tendon repair on muscle alterations.

    PubMed

    Uhthoff, Hans K; Coletta, Elizabeth; Trudel, Guy

    2014-11-01

    To investigate the impacts of delayed repairs of a supraspinatus tendon tear on the supraspinatus muscle, we used an animal model data from two previously published studies in which one supraspinatus (SSP) tendon was detached. In one cohort, the rabbits were killed in groups of 10 at 4, 8, and 12 weeks. In the other cohort, a repair was done at these time points, 12 rabbits each, and the animals killed were 12 weeks later. SSP fossa volume (Muscle belly plus extramuscular fat [e-fat] volume), percentage of intramuscular fat (i-fat), and muscle tissue volume (muscle belly volume minus i-fat), as well as CT determination of e-fat and i-fat of both cohorts, were compared. Fossa volume increased (p < 0.05). Muscle belly and muscle tissue volumes did not increase after repair (p > 0.05), but early repair prevented further volume losses, a fact not seen after 8 and 12 weeks delay of repair. No reversal of e-fat or of i-fat occurred, in fact i-fat almost doubled after 4 weeks delay of repair (p < 0.05). CT studies confirmed the fat results. We conclude that early repair prevented loss of muscle belly and muscle tissue volumes, but that it has no positive influence on fat accumulation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  5. Alterations in multidimensional motor unit number index of hand muscles after incomplete cervical spinal cord injury.

    PubMed

    Li, Le; Li, Xiaoyan; Liu, Jie; Zhou, Ping

    2015-01-01

    The objective of this study was to apply a novel multidimensional motor unit number index (MD-MUNIX) technique to examine hand muscles in patients with incomplete cervical spinal cord injury (SCI). The MD-MUNIX was estimated from the compound muscle action potential (CMAP) and different levels of surface interference pattern electromyogram (EMG) at multiple directions of voluntary isometric muscle contraction. The MD-MUNIX was applied in the first dorsal interosseous (FDI), thenar and hypothenar muscles of SCI (n = 12) and healthy control (n = 12) subjects. The results showed that the SCI subjects had significantly smaller CMAP and MD-MUNIX in all the three examined muscles, compared to those derived from the healthy control subjects. The multidimensional motor unit size index (MD-MUSIX) demonstrated significantly larger values for the FDI and hypothenar muscles in SCI subjects than those from healthy control subjects, whereas the MD-MUSIX enlargement was marginally significant for the thenar muscles. The findings from the MD-MUNIX analyses provide an evidence of motor unit loss in hand muscles of cervical SCI patients, contributing to hand function deterioration.

  6. Differences in Age-Related Alterations in Muscle Contraction Properties in Rat Tongue and Hindlimb

    ERIC Educational Resources Information Center

    Connor, Nadine P.; Ota, Fumikazu; Nagai, Hiromi; Russell, John A.; Leverson, Glen

    2008-01-01

    Purpose: Because of differences in muscle architecture and biomechanics, the purpose of this study was to determine whether muscle contractile properties of rat hindlimb and tongue were differentially affected by aging. Method: Deep peroneal and hypoglossal nerves were stimulated in 6 young and 7 old Fischer 344-Brown Norway rats to allow…

  7. Differences in Age-Related Alterations in Muscle Contraction Properties in Rat Tongue and Hindlimb

    ERIC Educational Resources Information Center

    Connor, Nadine P.; Ota, Fumikazu; Nagai, Hiromi; Russell, John A.; Leverson, Glen

    2008-01-01

    Purpose: Because of differences in muscle architecture and biomechanics, the purpose of this study was to determine whether muscle contractile properties of rat hindlimb and tongue were differentially affected by aging. Method: Deep peroneal and hypoglossal nerves were stimulated in 6 young and 7 old Fischer 344-Brown Norway rats to allow…

  8. Alteration of Muscle Function After Electrical Stimulation Bout of Knee Extensors and Flexors

    PubMed Central

    Vanderthommen, Marc; Triffaux, Mylène; Demoulin, Christophe; Crielaard, Jean-Michel; Croisier, Jean-Louis

    2012-01-01

    The purpose was to study the effects on muscle function of an electrical stimulation bout applied unilaterally on thigh muscles in healthy male volunteers. One group (ES group, n = 10) received consecutively 100 isometric contractions of quadriceps and 100 isometric contractions of hamstrings (on-off ratio 6-6 s) induced by neuromuscular electrical stimulations (NMES). Changes in muscle torque, muscle soreness (0-10 VAS), muscle stiffness and serum creatine kinase (CK) activity were assessed before the NMES exercise (pre-ex) as well as 24h (d+1), 48h (d+2) and 120h (d+5) after the bout. A second group (control group, n = 10) were submitted to the same test battery than the ES group and with the same time-frame. The between-group comparison indicated a significant increase in VAS scores and in serum levels of CK only in the ES group. In the ES group, changes were more pronounced in hamstrings than in quadriceps and peaked at d+2 (quadriceps VAS scores = 2.20 ± 1.55 a.u. (0 at pre-ex); hamstrings VAS scores = 3.15 ± 2.14 a.u. (0 at pre-ex); hip flexion angle = 62 ± 5° (75 ± 6° at pre-ex); CK activity = 3021 ± 2693 IU·l-1 (136 ± 50 IU·l-1 at pre-ex)). The results of the present study suggested the occurrence of muscle damage that could have been induced by the peculiar muscle recruitment in NMES and the resulting overrated mechanical stress. The sensitivity to the damaging effects of NMES appeared higher in the hamstrings than in quadriceps muscles. Key points A stimulation bout of quadriceps and hamstrings that reflects usual application of NMES, increases indirect markers of muscle damage (muscle soreness, muscle weakness and stiffness and serum CK activity). The occurrence of muscle damage could have been induced by the peculiar muscle recruitment in NMES and the resulting overrated mechanical stress. The sensitivity to the damaging effects of NMES appears higher in the hamstrings than in quadriceps muscles. PMID:24150067

  9. Altered satellite cell dynamics accompany skeletal muscle atrophy during chronic illness, disuse, and aging.

    PubMed

    McKenna, Colleen F; Fry, Christopher S

    2017-08-08

    This review explores recent research investigating the contribution of satellite cells (skeletal muscle stem cells) during muscle fiber atrophy as seen in periods of disuse, illness, and aging. Studies indicate reduced satellite cell activity and density in a variety of acute and chronic conditions characterized by robust muscle wasting. The direct contribution of satellite cells to unloading/denervation and chronic illness-induced atrophy remains controversial. Inflammation that accompanies acute trauma and illness likely impedes proper satellite cell differentiation and myogenesis, promoting the rapid onset of muscle wasting in these conditions. Transgenic mouse studies provide surprising evidence that age-related declines in satellite cell function and abundance are not causally related to the onset of sarcopenia in sedentary animals. Recent clinical and preclinical studies indicate reduced abundance and dysregulated satellite cell activity that accompany muscle atrophy during periods of disuse, illness, and aging, providing evidence for their therapeutic potential.

  10. Obesity Appears to Be Associated With Altered Muscle Protein Synthetic and Breakdown Responses to Increased Nutrient Delivery in Older Men, but Not Reduced Muscle Mass or Contractile Function.

    PubMed

    Murton, Andrew J; Marimuthu, Kanagaraj; Mallinson, Joanne E; Selby, Anna L; Smith, Kenneth; Rennie, Michael J; Greenhaff, Paul L

    2015-09-01

    Obesity is increasing, yet despite the necessity of maintaining muscle mass and function with age, the effect of obesity on muscle protein turnover in older adults remains unknown. Eleven obese (BMI 31.9 ± 1.1 kg · m(-2)) and 15 healthy-weight (BMI 23.4 ± 0.3 kg · m(-2)) older men (55-75 years old) participated in a study that determined muscle protein synthesis (MPS) and leg protein breakdown (LPB) under postabsorptive (hypoinsulinemic-euglycemic clamp) and postprandial (hyperinsulinemic hyperaminoacidemic-euglycemic clamp) conditions. Obesity was associated with systemic inflammation, greater leg fat mass, and patterns of mRNA expression consistent with muscle deconditioning, whereas leg lean mass, strength, and work done during maximal exercise were no different. Under postabsorptive conditions, MPS and LPB were equivalent between groups, whereas insulin and amino acid administration increased MPS in only healthy-weight subjects and was associated with lower leg glucose disposal (LGD) (63%) in obese men. Blunting of MPS in the obese men was offset by an apparent decline in LPB, which was absent in healthy-weight subjects. Lower postprandial LGD in obese subjects and blunting of MPS responses to amino acids suggest that obesity in older adults is associated with diminished muscle metabolic quality. This does not, however, appear to be associated with lower leg lean mass or strength. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  11. Alterations at the Cross-Bridge Level Are Associated with a Paradoxical Gain of Muscle Function In Vivo in a Mouse Model of Nemaline Myopathy

    PubMed Central

    Gineste, Charlotte; Ottenheijm, Coen; Le Fur, Yann; Banzet, Sébastien; Pecchi, Emilie; Vilmen, Christophe; Cozzone, Patrick J.; Koulmann, Nathalie; Hardeman, Edna C.; Bendahan, David; Gondin, Julien

    2014-01-01

    Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding α-tropomyosinslow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic (Tg) mice carrying the TPM3Met9Arg mutation, we investigated carefully the effect of the Met9Arg mutation in 8–9 month-old Tg(TPM3)Met9Arg mice on muscle function using a multiscale methodological approach including skinned muscle fibers analysis and in vivo investigations by magnetic resonance imaging and 31-phosphorus magnetic resonance spectroscopy. While in vitro maximal force production was reduced in Tg(TPM3)Met9Arg mice as compared to controls, in vivo measurements revealed an improved mechanical performance in the transgenic mice as compared to the former. The reduced in vitro muscle force might be related to alterations occuring at the cross-bridges level with muscle-specific underlying mechanisms. In vivo muscle improvement was not associated with any changes in either muscle volume or energy metabolism. Our findings indicate that TPM3(Met9Arg) mutation leads to a mild muscle weakness in vitro related to an alteration at the cross-bridges level and a paradoxical gain of muscle function in vivo. These results clearly point out that in vitro alterations are muscle-dependent and do not necessarily translate into similar changes in vivo. PMID:25268244

  12. Alterations at the cross-bridge level are associated with a paradoxical gain of muscle function in vivo in a mouse model of nemaline myopathy.

    PubMed

    Gineste, Charlotte; Ottenheijm, Coen; Le Fur, Yann; Banzet, Sébastien; Pecchi, Emilie; Vilmen, Christophe; Cozzone, Patrick J; Koulmann, Nathalie; Hardeman, Edna C; Bendahan, David; Gondin, Julien

    2014-01-01

    Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding α-tropomyosin slow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic (Tg) mice carrying the TPM3Met9Arg mutation, we investigated carefully the effect of the Met9Arg mutation in 8-9 month-old Tg(TPM3)Met9Arg mice on muscle function using a multiscale methodological approach including skinned muscle fibers analysis and in vivo investigations by magnetic resonance imaging and 31-phosphorus magnetic resonance spectroscopy. While in vitro maximal force production was reduced in Tg(TPM3)Met9Arg mice as compared to controls, in vivo measurements revealed an improved mechanical performance in the transgenic mice as compared to the former. The reduced in vitro muscle force might be related to alterations occurring at the cross-bridges level with muscle-specific underlying mechanisms. In vivo muscle improvement was not associated with any changes in either muscle volume or energy metabolism. Our findings indicate that TPM3(Met9Arg) mutation leads to a mild muscle weakness in vitro related to an alteration at the cross-bridges level and a paradoxical gain of muscle function in vivo. These results clearly point out that in vitro alterations are muscle-dependent and do not necessarily translate into similar changes in vivo.

  13. Alterations of cAMP-dependent signaling in dystrophic skeletal muscle

    PubMed Central

    Rudolf, Rüdiger; Khan, Muzamil M.; Lustrino, Danilo; Labeit, Siegfried; Kettelhut, Ísis C.; Navegantes, Luiz C. C.

    2013-01-01

    Autonomic regulation processes in striated muscles are largely mediated by cAMP/PKA-signaling. In order to achieve specificity of signaling its spatial-temporal compartmentation plays a critical role. We discuss here how specificity of cAMP/PKA-signaling can be achieved in skeletal muscle by spatio-temporal compartmentation. While a microdomain containing PKA type I in the region of the neuromuscular junction (NMJ) is important for postsynaptic, activity-dependent stabilization of the nicotinic acetylcholine receptor (AChR), PKA type I and II microdomains in the sarcomeric part of skeletal muscle are likely to play different roles, including the regulation of muscle homeostasis. These microdomains are due to specific A-kinase anchoring proteins, like rapsyn and myospryn. Importantly, recent evidence indicates that compartmentation of the cAMP/PKA-dependent signaling pathway and pharmacological activation of cAMP production are aberrant in different skeletal muscles disorders. Thus, we discuss here their potential as targets for palliative treatment of certain forms of dystrophy and myasthenia. Under physiological conditions, the neuropeptide, α-calcitonin-related peptide, as well as catecholamines are the most-mentioned natural triggers for activating cAMP/PKA signaling in skeletal muscle. While the precise domains and functions of these first messengers are still under investigation, agonists of β2-adrenoceptors clearly exhibit anabolic activity under normal conditions and reduce protein degradation during atrophic periods. Past and recent studies suggest direct sympathetic innervation of skeletal muscle fibers. In summary, the organization and roles of cAMP-dependent signaling in skeletal muscle are increasingly understood, revealing crucial functions in processes like nerve-muscle interaction and muscle trophicity. PMID:24146652

  14. Nitrite attenuates ischemia-reperfusion-induced microcirculatory alterations and mitochondrial dysfunction in the microvasculature of skeletal muscle.

    PubMed

    Wang, Wei Z; Fang, Xin-Hua; Stephenson, Linda L; Zhang, Xinlan; Williams, Shelley J; Baynosa, Richard C; Khiabani, Kayvan T; Zamboni, William A

    2011-10-01

    Recently, nitrite has been rediscovered as a physiologically relevant storage reservoir of nitric oxide in blood and it can readily be converted to nitric oxide under hypoxic and acidic conditions. In this study, the authors evaluated the therapeutic efficacy of nitrite on reperfusion-induced microcirculatory alterations and mitochondrial dysfunction in the microvasculature of skeletal muscle. The authors used a vascular pedicle isolated rat cremaster model that underwent 4 hours of warm ischemia followed by 2 hours or 17 hours of reperfusion. At 5 minutes before reperfusion, normal saline, sodium nitrite (0.20 μM/minute/kg), or nitrite mixed with 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (potassium salt) (0.2 mg/minute/kg) was infused into the microcirculation of ischemic cremaster by means of intraarterial infusion. Ischemia-reperfusion-induced microcirculatory alterations were measured after 2 hours of reperfusion. Microvasculature of the cremaster muscle including the vascular pedicle was harvested to determine the mitochondrial dysfunction. The blood concentration of methemoglobin was also measured to determine the toxicity of nitrite. The authors found that nitrite significantly attenuated ischemia-reperfusion-induced vasoconstriction, arteriole stagnation, and capillary no-reflow in the early phase of reperfusion and the depolarization of mitochondrial membrane potential and cytochrome c release in the late phase of reperfusion. Nitrite-induced protection was significantly blocked by a nitric oxide scavenger (potassium salt). The methemoglobin results showed that the doses of nitrite we used in the present study were safe. The supplementation of a low dose of nitrite, directly into the microcirculation of ischemic muscle through local intraarterial infusion, significantly attenuated ischemia-reperfusion-induced microcirculatory alterations in vivo and mitochondrial dysfunction in vitro in the microvasculature of skeletal

  15. Are muscle activation patterns altered during shod and barefoot running with a forefoot footfall pattern?

    PubMed

    Ervilha, Ulysses Fernandes; Mochizuki, Luis; Figueira, Aylton; Hamill, Joseph

    2016-09-14

    This study aimed to investigate the activation of lower limb muscles during barefoot and shod running with forefoot or rearfoot footfall patterns. Nine habitually shod runners were asked to run straight for 20 m at self-selected speed. Ground reaction forces and thigh and shank muscle surface electromyographic (EMG) were recorded. EMG outcomes (EMG intensity [iEMG], latency between muscle activation and ground reaction force, latency between muscle pairs and co-activation index between muscle pairs) were compared across condition (shod and barefoot), running cycle epochs (pre-strike, strike, propulsion) and footfall (rearfoot and forefoot) by ANOVA. Condition affected iEMG at pre-strike epoch. Forefoot and rearfoot strike patterns induced different EMG activation time patterns affecting co-activation index for pairs of thigh and shank muscles. All these timing changes suggest that wearing shoes or not is less important for muscle activation than the way runners strike the foot on the ground. In conclusion, the guidance for changing external forces applied on lower limbs should be pointed to the question of rearfoot or forefoot footfall patterns.

  16. An Acute Bout of Barefoot Running Alters Lower-limb Muscle Activation for Minimalist Shoe Users.

    PubMed

    Snow, N J; Basset, F A; Byrne, J

    2016-05-01

    Despite the abundance of barefoot running-related research, there have been no electromyography studies evaluating the effects of this mode of exercise on habitual users of minimalist footwear. The present study investigated differences in muscle activation during acute bouts of barefoot and shod running, in minimalist shoe users. 8 male participants ran on a motorized treadmill for 10 min under both conditions, at 70% maximal aerobic speed. Electromyographic data were sampled from the biceps femoris, gluteus maximus, gastrocnemius medialis, tibialis anterior, and vastus lateralis during both swing and stance. Root-mean-square analysis of electromyographic data was conducted to compare muscle activation between conditions. During stance, barefoot running resulted in greater muscle activity in gastrocnemius medialis and gluteus maximus, and lower muscle activity in tibialis anterior. During swing, barefoot running resulted in increased muscle activity in vastus lateralis and gastrocnemius medialus. These results indicate that, for minimalist shoe users, an acute bout of barefoot running results in significantly different lower-limb muscle activity. Increased activation in the above muscles presents a possible mechanism for injury, which should be considered during exercise prescription.

  17. Alterations in Osteopontin Modify Muscle Size in Females in Both Humans and Mice

    PubMed Central

    Hoffman, Eric P.; Gordish-Dressman, Heather; McLane, Virginia D.; Devaney, Joseph M.; Thompson, Paul D.; Visich, Paul; Gordon, Paul M.; Pescatello, Linda S.; Zoeller, Robert F.; Moyna, Niall M.; Angelopoulos, Theodore J.; Pegoraro, Elena; Cox, Gregory A.; Clarkson, Priscilla M.

    2013-01-01

    PURPOSE An osteopontin (OPN; SPP1) gene promoter polymorphism modifies disease severity in Duchenne muscular dystrophy, and we hypothesized that it might also modify muscle phenotypes in healthy volunteers. METHODS Gene association studies were carried out for OPN (rs28357094) in the FAMuSS cohort (n=752; age 23.7±5.7 yrs). Phenotypes studied included muscle size (MRI), strength, and response to supervised resistance training. We also studied 147 young adults that had carried out a bout of eccentric elbow exercise (age 24.0 ± 5.2 yrs). Phenotypes analyzed included strength, soreness, and serum muscle enzymes. RESULTS In the FAMuSS cohort, the G allele was associated with 17% increase in baseline upper arm muscle volume only in women (F=26.32; p=5.32 × 10−7), explaining 5% of population variance. In the eccentric damage cohort, weak associations of the G allele were seen in women with both baseline myoglobin, and elevated CK. Sexually dimorphic effects of OPN on muscle were also seen in OPN null mice. Five of seven muscle groups examined showed smaller size in OPN null female mice, whereas two were smaller in males. Query of OPN gene transcription after experimental muscle damage in mice showed rapid induction within 12 hrs (100-fold increase from baseline), followed by sustained high level expression through 16 days of regeneration before falling to back to baseline. CONCLUSION OPN is a sexually dimorphic modifier of muscle size in normal humans and mice, and responds to muscle damage. The OPN gene is known to be estrogen responsive, and this may explain the female-specific genotype effects in adult volunteers. PMID:23274598

  18. Altered vascular smooth muscle function in the ApoE knockout mouse during the progression of atherosclerosis.

    PubMed

    Ewart, Marie-Ann; Kennedy, Simon; Macmillan, Debbi; Raja, Abhirami L N; Watt, Ian M; Currie, Susan

    2014-05-01

    Relaxation of vascular smooth muscle (VSM) requires re-uptake of cytosolic Ca(2+) into the sarcoplasmic reticulum (SR) via the Sarco/Endoplasmic Reticulum Ca(2+) ATPase (SERCA), or extrusion via the Plasma Membrane Ca(2+) ATPase (PMCA) or sodium Ca(2+) exchanger (NCX). Peroxynitrite, a reactive species formed in vascular inflammatory diseases, upregulates SERCA activity to induce relaxation but, chronically, can contribute to atherogenesis and altered vascular function by escalating endoplasmic reticulum stress. Our objectives were to determine if peroxynitrite-induced relaxation and Ca(2+) handling processes within vascular smooth muscle cells were altered as atherosclerosis develops. Aortae from control and ApoE(-/-) mice were studied histologically, functionally and for protein expression levels of SERCA and PMCA. Ca(2+) responses were assessed in dissociated aortic smooth muscle cells in the presence and absence of extracellular Ca(2+). Relaxation to peroxynitrite was concentration-dependent and endothelium-independent. The abilities of the SERCA blocker thapsigargin and the PMCA inhibitor carboxyeosin to block this relaxation were altered during fat feeding and plaque progression. SERCA levels were progressively reduced, while PMCA expression was upregulated. In ApoE(-/-) VSM cells, increases in cytosolic Ca(2+) [Ca(2+)]c in response to SERCA blockade were reduced, while SERCA-independent Ca(2+) clearance was faster compared to control. As atherosclerosis develops in the ApoE(-/-) mouse, expression and function of Ca(2+) handling proteins are altered. Up-regulation of Ca(2+) removal via PMCA may offer a potential compensatory mechanism to help normalise the dysfunctional relaxation observed during disease progression. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  19. Characterization of muscle alteration in oral submucous fibrosis-seeking new evidence

    PubMed Central

    Urs, Aadithya-Basavaraj; Augustine, Jeyaseelan; Kumar, Priya

    2015-01-01

    Background The aim of the study was to assess the progression of Oral Submucous Fibrosis (OSF) by investigating the correlation between clinical mouth opening and muscle-epithelial distance in tissue sections. Characterization of changes involving muscle was ascertained. Material and Methods 50 cases and 10 controls were included in this case-control study. Inter-incisal mouth opening was measured and classified according to Lai et al. as Group A (more than 35mm), Group B (30 to 35mm), Group C (20 to 30mm), Group D (less than 20mm). Histopathological sections were graded as very early, early, moderately advanced, advanced OSF. Muscle-epithelial distance was calculated using image analysis software. The four most common degenerative changes observed in muscles, namely fragmentation, highly eosinophilic areas with loss of striations, nucleus internalization and multiple pyknotic nuclei were also assessed. Results Comparisons of muscle-epithelial distance were made between the clinical and histopathological groups to those of controls. The mean muscle-epithelial distance was: Group A-626.8±309.36 µm, B-827.5±549.72 µm, C-673.2±321.93 µm, D-439.9±173.84µm, Controls-1222.19 ±441.7µm. Post-hoc Bonferroni Test revealed a statistically significant reduction in the muscle-epithelial distance in Group C (p-value = 0.001) and D (p-value = 0.001) as compared to controls. The mean muscle-epithelial distance in very early, early, moderately advanced and advanced OSF was 732.73±232.81µm, 726.54±361.63 µm, 548.36±273.13 and 172.40±58.41 µm respectively. Highly significant difference in muscle-epithelial distance was seen between controls as compared to early (p-value =0.002), moderately advanced (p-value = 0.001) and advanced OSF (p-value = 0.001. Fragmentation and highly eosinophilic areas were invariably noticed in advanced OSF. Multiple pyknotic nuclei were variable with no specificity. Conclusions Reduction in muscle-epithelial distance may prove to be a

  20. Lengthening But Not Shortening History of Paraspinal Muscle Spindles in the Low Back Alters Their Dynamic Sensitivity

    PubMed Central

    Cao, Dong-Yuan

    2011-01-01

    Proprioception is considered important for maintaining spinal stability and for controlling posture and movement in the low back. Previous studies demonstrate the presence of thixotropic properties in lumbar muscle spindles, wherein a vertebra's positional history alters spindle responsiveness to position and movement. This study investigated whether a vertebra's movement history affects the velocity sensitivity of paraspinal muscle spindles in the low back. Afferent activity from multifidus and longissimus muscle spindles was recorded in the L6 dorsal root in 30 anesthetized cats. To alter movement history, a feedback-controlled motor attached to the L6 spinous process held (conditioned for 4 s) the L6 vertebra at an intermediate position or at positions that either lengthened or shortened the muscles. With the vertebra returned to the intermediate position, resting spindle discharge was measured over the next 0.5 s (static test) and then during a dynamic test consisting of ramp vertebral movement at four velocities (0.2, 0.5, 1.0, 2.0 mm/s). Spindle activity during the tests was measured relative to hold-intermediate. For both tests, hold-long decreased and hold-short increased muscle spindle responsiveness. For the static test position responsiveness was not different among the velocity protocols for either hold-long or hold-short (P = 0.42 and 0.24, respectively). During the dynamic test, hold-long conditioning significantly decreased [F(3,119) = 7.99, P < 0.001] spindle responsiveness to increasing velocity. Mean velocity sensitivity was 4.44, 3.39, and 1.41 (impulses/s)/(mm/s) for the hold-short, hold-intermediate, and hold-long protocols, respectively. The nearly 2.5-fold decrease in velocity sensitivity following hold-long was significantly less than that for either hold-intermediate (P = 0.005) or hold-short conditioning (P < 0.001). Hold-short conditioning had little effect on velocity responses during the dynamic test [F(3,119) = 0.23, P = 0.87]. In

  1. Carbohydrate/fat ratio in the diet alters histone acetylation on the sucrase-isomaltase gene and its expression in mouse small intestine.

    PubMed

    Honma, Kazue; Mochizuki, Kazuki; Goda, Toshinao

    2007-06-15

    A diet with a high carbohydrate/fat ratio enhances jejunal SI gene expression. Using ChIP assay, we revealed that the acetylation of histone H3 on transcriptional region and H4 on promoter region, respectively, of mouse SI gene are high. The acetylation of histone H3 and H4 as well as binding of HNF-1 and Cdx-2 on SI gene, was enhanced by increase in carbohydrate/fat ratio in the diet. These suggest that induction of SI gene by the diet rich in carbohydrate is associated with acetylation of histone H3 and H4 as well as binding of HNF-1 and Cdx-2 on SI gene.

  2. Altering prosthetic foot stiffness influences foot and muscle function during below-knee amputee walking: a modeling and simulation analysis.

    PubMed

    Fey, Nicholas P; Klute, Glenn K; Neptune, Richard R

    2013-02-22

    Most prosthetic feet are designed to improve amputee gait by storing and releasing elastic energy during stance. However, how prosthetic foot stiffness influences muscle and foot function is unclear. Identifying these relationships would provide quantitative rationale for prosthetic foot prescription that may lead to improved amputee gait. The purpose of this study was to identify the influence of altered prosthetic foot stiffness on muscle and foot function using forward dynamics simulations of amputee walking. Three 2D muscle-actuated forward dynamics simulations of unilateral below-knee amputee walking with a range of foot stiffness levels were generated, and muscle and prosthetic foot contributions to body support and propulsion and residual leg swing were quantified. As stiffness decreased, the prosthetic keel provided increased support and braking (negative propulsion) during the first half of stance while the heel contribution to support decreased. During the second half of stance, the keel provided decreased propulsion and increased support. In addition, the keel absorbed less power from the leg, contributing more to swing initiation. Thus, several muscle compensations were necessary. During the first half of stance, the residual leg hamstrings provided decreased support and increased propulsion. During the second half of stance, the intact leg vasti provided increased support and the residual leg rectus femoris transferred increased energy from the leg to the trunk for propulsion. These results highlight the influence prosthetic foot stiffness has on muscle and foot function throughout the gait cycle and may aid in prescribing feet of appropriate stiffness. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Fourier analysis of wing beat signals: assessing the effects of genetic alterations of flight muscle structure in Diptera.

    PubMed Central

    Hyatt, C J; Maughan, D W

    1994-01-01

    A method for determining and analyzing the wing beat frequency in Diptera is presented. This method uses an optical tachometer to measure Diptera wing movement during flight. The resulting signal from the optical measurement is analyzed using a Fast Fourier Transform (FFT) technique, and the dominant frequency peak in the Fourier spectrum is selected as the wing beat frequency. Also described is a method for determining quantitatively the degree of variability of the wing beat frequency about the dominant frequency. This method is based on determination of a quantity called the Hindex, which is derived using data from the FFT analysis. Calculation of the H index allows computer-based selection of the most suitable segment of recorded data for determination of the representative wing beat frequency. Experimental data suggest that the H index can also prove useful in examining wing beat frequency variability in Diptera whose flight muscle structure has been genetically altered. Examples from Drosophila indirect flight muscle studies as well as examples of artificial data are presented to illustrate the method. This method fulfills a need for a standardized method for determining wing beat frequencies and examining wing beat frequency variability in insects whose flight muscles have been altered by protein engineering methods. PMID:7811927

  4. Are Modular Activations Altered in Lower Limb Muscles of Persons with Multiple Sclerosis during Walking? Evidence from Muscle Synergies and Biomechanical Analysis

    PubMed Central

    Lencioni, Tiziana; Jonsdottir, Johanna; Cattaneo, Davide; Crippa, Alessandro; Gervasoni, Elisa; Rovaris, Marco; Bizzi, Emilio; Ferrarin, Maurizio

    2016-01-01

    Background: Persons with Multiple Sclerosis frequently have gait deficits that lead to diminished activities of daily living. Identification of motoneuron activity patterns may elucidate new insight into impaired locomotor coordination and underlying neural systems. The aim of the present study was to investigate muscle synergies, identified by motor modules and their activation profiles, in persons with Multiple Sclerosis (PwMS) during walking compared to those of healthy subjects (HS), as well as, exploring relationship of muscle synergies with walking ability of PwMS. Methods: Seventeen PwMS walked at their natural speed while 12 HS walked at slower than their natural speeds in order to provide normative gait values at matched speeds (spatio-temporal, kinematic, and kinetic parameters and electromyography signals). Non-negative matrix factorization was used to identify muscle synergies from eight muscles. Pearson's correlation coefficient was used to evaluate the similarity of motor modules between PwMS and HS. To assess differences in module activations, each module's activation timing was integrated over 100% of gait cycle and the activation percentage was computed in six phases. Results: Fifty-nine% of PwMS and 58% of HS had 4 modules while the remaining of both populations had 3 modules. Module 2 (related to soleus, medial, and lateral gastrocnemius primarily involved in mid and terminal stance) and Module 3 (related to tibialis anterior and rectus femoris primarily involved in early stance, and early and late swing) were comparable across all subjects regardless of synergies number. PwMS had shorter stride length, longer double support phase and push off deficit with respect to HS (p < 0.05). The alterations of activation timing profiles of specific modules in PwMS were associated with their walking deficits (e.g., the reduction of Module 2 activation percentage index in terminal stance, PwMS 35.55 ± 13.23 vs. HS 50.51 ± 9.13% p < 0.05, and the push off

  5. Are Modular Activations Altered in Lower Limb Muscles of Persons with Multiple Sclerosis during Walking? Evidence from Muscle Synergies and Biomechanical Analysis.

    PubMed

    Lencioni, Tiziana; Jonsdottir, Johanna; Cattaneo, Davide; Crippa, Alessandro; Gervasoni, Elisa; Rovaris, Marco; Bizzi, Emilio; Ferrarin, Maurizio

    2016-01-01

    Background: Persons with Multiple Sclerosis frequently have gait deficits that lead to diminished activities of daily living. Identification of motoneuron activity patterns may elucidate new insight into impaired locomotor coordination and underlying neural systems. The aim of the present study was to investigate muscle synergies, identified by motor modules and their activation profiles, in persons with Multiple Sclerosis (PwMS) during walking compared to those of healthy subjects (HS), as well as, exploring relationship of muscle synergies with walking ability of PwMS. Methods: Seventeen PwMS walked at their natural speed while 12 HS walked at slower than their natural speeds in order to provide normative gait values at matched speeds (spatio-temporal, kinematic, and kinetic parameters and electromyography signals). Non-negative matrix factorization was used to identify muscle synergies from eight muscles. Pearson's correlation coefficient was used to evaluate the similarity of motor modules between PwMS and HS. To assess differences in module activations, each module's activation timing was integrated over 100% of gait cycle and the activation percentage was computed in six phases. Results: Fifty-nine% of PwMS and 58% of HS had 4 modules while the remaining of both populations had 3 modules. Module 2 (related to soleus, medial, and lateral gastrocnemius primarily involved in mid and terminal stance) and Module 3 (related to tibialis anterior and rectus femoris primarily involved in early stance, and early and late swing) were comparable across all subjects regardless of synergies number. PwMS had shorter stride length, longer double support phase and push off deficit with respect to HS (p < 0.05). The alterations of activation timing profiles of specific modules in PwMS were associated with their walking deficits (e.g., the reduction of Module 2 activation percentage index in terminal stance, PwMS 35.55 ± 13.23 vs. HS 50.51 ± 9.13% p < 0.05, and the push off

  6. Exercise-Induced Skeletal Muscle Adaptations Alter the Activity of Adipose Progenitor Cells.

    PubMed

    Zeve, Daniel; Millay, Douglas P; Seo, Jin; Graff, Jonathan M

    2016-01-01

    Exercise decreases adiposity and improves metabolic health; however, the physiological and molecular underpinnings of these phenomena remain unknown. Here, we investigate the effect of endurance training on adipose progenitor lineage commitment. Using mice with genetically labeled adipose progenitors, we show that these cells react to exercise by decreasing their proliferation and differentiation potential. Analyses of mouse models that mimic the skeletal muscle adaptation to exercise indicate that muscle, in a non-autonomous manner, regulates adipose progenitor homeostasis, highlighting a role for muscle-derived secreted factors. These findings support a humoral link between skeletal muscle and adipose progenitors and indicate that manipulation of adipose stem cell function may help address obesity and diabetes.

  7. Alterations to mitochondrial fatty-acid use in skeletal muscle after chronic exposure to hypoxia depend on metabolic phenotype.

    PubMed

    Malgoyre, Alexandra; Chabert, Clovis; Tonini, Julia; Koulmann, Nathalie; Bigard, Xavier; Sanchez, Hervé

    2017-03-01

    We investigated the effects of chronic hypoxia on the maximal use of and sensitivity of mitochondria to different substrates in rat slow-oxidative (soleus, SOL) and fast-glycolytic (extensor digitorum longus, EDL) muscles. We studied mitochondrial respiration in situ in permeabilized myofibers, using pyruvate, octanoate, palmitoyl-carnitine (PC), or palmitoyl-coenzyme A (PCoA). The hypophagia induced by hypoxia may also alter metabolism. Therefore, we used a group of pair-fed rats (reproducing the same caloric restriction, as observed in hypoxic animals), in addition to the normoxic control fed ad libitum. The resting respiratory exchange ratio decreased after 21 days of exposure to hypobaric hypoxia (simulated elevation of 5,500 m). The respiration supported by pyruvate and octanoate were unaffected. In contrast, the maximal oxidative respiratory rate for PCoA, the transport of which depends on carnitine palmitoyltransferase 1 (CPT-1), decreased in the rapid-glycolytic EDL and increased in the slow-oxidative SOL, although hypoxia improved affinity for this substrate in both muscle types. PC and PCoA were oxidized similarly in normoxic EDL, whereas chronic hypoxia limited transport at the CPT-1 step in this muscle. The effects of hypoxia were mediated by caloric restriction in the SOL and by hypoxia itself in the EDL. We conclude that improvements in mitochondrial affinity for PCoA, a physiological long-chain fatty acid, would facilitate fatty-acid use at rest after chronic hypoxia independently of quantitative alterations of mitochondria. Conversely, decreasing the maximal oxidation of PCoA in fast-glycolytic muscles would limit fatty-acid use during exercise.NEW & NOTEWORTHY Affinity for low concentrations of long-chain fatty acids (LCFA) in mitochondria skeletal muscles increases after chronic hypoxia. Combined with a lower respiratory exchange ratio, this suggests facility for fatty acid utilization at rest. This fuel preference is related to caloric

  8. Alteration of muscle function after electrical stimulation bout of knee extensors and flexors.

    PubMed

    Vanderthommen, Marc; Triffaux, Mylène; Demoulin, Christophe; Crielaard, Jean-Michel; Croisier, Jean-Louis

    2012-01-01

    The purpose was to study the effects on muscle function of an electrical stimulation bout applied unilaterally on thigh muscles in healthy male volunteers. One group (ES group, n = 10) received consecutively 100 isometric contractions of quadriceps and 100 isometric contractions of hamstrings (on-off ratio 6-6 s) induced by neuromuscular electrical stimulations (NMES). Changes in muscle torque, muscle soreness (0-10 VAS), muscle stiffness and serum creatine kinase (CK) activity were assessed before the NMES exercise (pre-ex) as well as 24h (d+1), 48h (d+2) and 120h (d+5) after the bout. A second group (control group, n = 10) were submitted to the same test battery than the ES group and with the same time-frame. The between-group comparison indicated a significant increase in VAS scores and in serum levels of CK only in the ES group. In the ES group, changes were more pronounced in hamstrings than in quadriceps and peaked at d+2 (quadriceps VAS scores = 2.20 ± 1.55 a.u. (0 at pre-ex); hamstrings VAS scores = 3.15 ± 2.14 a.u. (0 at pre-ex); hip flexion angle = 62 ± 5° (75 ± 6° at pre-ex); CK activity = 3021 ± 2693 IU·l(-1) (136 ± 50 IU·l(-1) at pre-ex)). The results of the present study suggested the occurrence of muscle damage that could have been induced by the peculiar muscle recruitment in NMES and the resulting overrated mechanical stress. The sensitivity to the damaging effects of NMES appeared higher in the hamstrings than in quadriceps muscles.

  9. Exercise training alters DNA methylation patterns in genes related to muscle growth and differentiation in mice.

    PubMed

    Kanzleiter, Timo; Jähnert, Markus; Schulze, Gunnar; Selbig, Joachim; Hallahan, Nicole; Schwenk, Robert Wolfgang; Schürmann, Annette

    2015-05-15

    The adaptive response of skeletal muscle to exercise training is tightly controlled and therefore requires transcriptional regulation. DNA methylation is an epigenetic mechanism known to modulate gene expression, but its contribution to exercise-induced adaptations in skeletal muscle is not well studied. Here, we describe a genome-wide analysis of DNA methylation in muscle of trained mice (n = 3). Compared with sedentary controls, 2,762 genes exhibited differentially methylated CpGs (P < 0.05, meth diff >5%, coverage >10) in their putative promoter regions. Alignment with gene expression data (n = 6) revealed 200 genes with a negative correlation between methylation and expression changes in response to exercise training. The majority of these genes were related to muscle growth and differentiation, and a minor fraction involved in metabolic regulation. Among the candidates were genes that regulate the expression of myogenic regulatory factors (Plexin A2) as well as genes that participate in muscle hypertrophy (Igfbp4) and motor neuron innervation (Dok7). Interestingly, a transcription factor binding site enrichment study discovered significantly enriched occurrence of CpG methylation in the binding sites of the myogenic regulatory factors MyoD and myogenin. These findings suggest that DNA methylation is involved in the regulation of muscle adaptation to regular exercise training. Copyright © 2015 the American Physiological Society.

  10. Jaw movement alters the reaction of human jaw muscles to incisor stimulation.

    PubMed

    Brinkworth, Russell S A; Türker, Kemal S

    2005-07-01

    The changes in the minimum time to consciously react (reaction time) and the order of jaw muscle recruitment to precisely controlled axial stimulation of the incisors during controlled jaw movements are not known. To this end, ten subjects were recruited to investigate the reaction time of bilateral temporalis and masseter muscles and bite force. Stimuli were delivered axially to the upper central incisors during active jaw closing and opening, and under static conditions. The results showed that the reaction time was increased an average of 35% during both jaw opening and closing movements when compared with static jaw conditions. The left temporalis was recruited approximately 10 ms before the right temporalis, whereas no significant side differences were found between the masseter muscles. The masseter muscles were recruited an average of 20 ms before the temporalis muscles during jaw closing, but no difference existed during opening. Under static conditions the reaction time in the bite force was approximately 16 ms longer than the left temporalis, but was not significantly different from the reaction time of any of the other muscles, indicating that, under the static conditions tested, the left temporalis was more often responsible for initiation of the mechanical reactions in the jaw. Because of active compensation, no force measurements were made during jaw movement. This study is a prerequisite for investigations into the modulation of reflexes during jaw movement, because a response to a stimulus commencing after the minimum reaction time may not be entirely reflex in origin.

  11. Pseudouridine synthase 1 deficient mice, a model for Mitochondrial Myopathy with Sideroblastic Anemia, exhibit muscle morphology and physiology alterations

    PubMed Central

    Mangum, Joshua E.; Hardee, Justin P.; Fix, Dennis K.; Puppa, Melissa J.; Elkes, Johnathon; Altomare, Diego; Bykhovskaya, Yelena; Campagna, Dean R.; Schmidt, Paul J.; Sendamarai, Anoop K.; Lidov, Hart G. W.; Barlow, Shayne C.; Fischel-Ghodsian, Nathan; Fleming, Mark D.; Carson, James A.; Patton, Jeffrey R.

    2016-01-01

    Mitochondrial myopathy with lactic acidosis and sideroblastic anemia (MLASA) is an oxidative phosphorylation disorder, with primary clinical manifestations of myopathic exercise intolerance and a macrocytic sideroblastic anemia. One cause of MLASA is recessive mutations in PUS1, which encodes pseudouridine (Ψ) synthase 1 (Pus1p). Here we describe a mouse model of MLASA due to mutations in PUS1. As expected, certain Ψ modifications were missing in cytoplasmic and mitochondrial tRNAs from Pus1−/− animals. Pus1−/− mice were born at the expected Mendelian frequency and were non-dysmorphic. At 14 weeks the mutants displayed reduced exercise capacity. Examination of tibialis anterior (TA) muscle morphology and histochemistry demonstrated an increase in the cross sectional area and proportion of myosin heavy chain (MHC) IIB and low succinate dehydrogenase (SDH) expressing myofibers, without a change in the size of MHC IIA positive or high SDH myofibers. Cytochrome c oxidase activity was significantly reduced in extracts from red gastrocnemius muscle from Pus1−/− mice. Transmission electron microscopy on red gastrocnemius muscle demonstrated that Pus1−/− mice also had lower intermyofibrillar mitochondrial density and smaller mitochondria. Collectively, these results suggest that alterations in muscle metabolism related to mitochondrial content and oxidative capacity may account for the reduced exercise capacity in Pus1−/− mice. PMID:27197761

  12. Increased susceptibility to ATP via alteration of P2X receptor function in dystrophic mdx mouse muscle cells.

    PubMed

    Yeung, Davy; Zablocki, Krzysztof; Lien, Chun-Fu; Jiang, Taiwen; Arkle, Stephen; Brutkowski, Wojciech; Brown, James; Lochmuller, Hanns; Simon, Joseph; Barnard, Eric A; Górecki, Dariusz C

    2006-04-01

    Pathological cellular hallmarks of Duchenne muscular dystrophy (DMD) include, among others, abnormal calcium homeostasis. Changes in the expression of specific receptors for extracellular ATP in dystrophic muscle have been recently documented: here, we demonstrate that at the earliest, myoblast stage of developing dystrophic muscle a purinergic dystrophic phenotype arises. In myoblasts of a dystrophin-negative muscle cell line established from the mdx mouse model of DMD but not in normal myoblasts, exposure to extracellular ATP triggered a strong increase in cytoplasmic Ca2+ concentrations. Influx of extracellular Ca2+ was stimulated by ATP and BzATP and inhibited by zinc, Coomassie Brilliant Blue-G, and KN-62, demonstrating activation of P2X7 receptors. Significant expression of P2X4 and P2X7 proteins was immunodetected in dystrophic myoblasts. Therefore, full-length dystrophin appears, surprisingly, to play an important role in myoblasts in controlling responses to ATP. Our results suggest that altered function of P2X receptors may be an important contributor to pathogenic Ca2+ entry in dystrophic mouse muscle and may have implications for the pathogenesis of muscular dystrophies. Treatments aiming at inhibition of specific ATP receptors could be of a potential therapeutic benefit.

  13. Altered gene expression and repressed markers of autophagy in skeletal muscle of insulin resistant patients with type 2 diabetes

    PubMed Central

    Møller, Andreas Buch; Kampmann, Ulla; Hedegaard, Jakob; Thorsen, Kasper; Nordentoft, Iver; Vendelbo, Mikkel Holm; Møller, Niels; Jessen, Niels

    2017-01-01

    This case-control study was designed to investigate the gene expression profile in skeletal muscle from severely insulin resistant patients with long-standing type 2 diabetes (T2D), and to determine associated signaling pathways. Gene expression profiles were examined by whole transcriptome, strand-specific RNA-sequencing and associated signaling was determined by western blot. We identified 117 differentially expressed gene transcripts. Ingenuity Pathway Analysis related these differences to abnormal muscle morphology and mitochondrial dysfunction. Despite a ~5-fold difference in plasma insulin, we did not observe any difference in phosphorylation of AKT or AS160, although other insulin-sensitive cascades, as mTOR/4EBP1, had retained their sensitivity. Autophagy-related gene (ATG14, RB1CC1/FIP200, GABARAPL1, SQSTM1/p62, and WIPI1) and protein (LC3BII, SQSTM1/p62 and ATG5) expression were decreased in skeletal muscle from the patients, and this was associated with a trend to increased phosphorylation of the insulin-sensitive regulatory transcription factor FOXO3a. These data show that gene expression is highly altered and related to mitochondrial dysfunction and abnormal morphology in skeletal muscle from severely insulin resistant patients with T2D, and that this is associated with decreased expression of autophagy-related genes and proteins. We speculate that prolonged treatment with high doses of insulin may suppress autophagy thereby generating a vicious cycle maintaining insulin resistance. PMID:28252104

  14. Clinicopathological Features and Immunohistochemical Alterations of Keratinocyte Proliferation, Melanocyte Density, Smooth Muscle Hyperplasia and Nerve Fiber Distribution in Becker's Nevus

    PubMed Central

    Sheng, Ping; Cheng, Yun-Long; Cai, Chuan-Chuan; Guo, Wei-Jin; Zhou, Ying; Shi, Ge

    2016-01-01

    Background Although Becker's nevus (BN) is a relatively common disease, the systematic studies of clinicopathological and immunohistochemical results are poorly reported. Objective To investigate the clinicopathological features and immunohistochemical alterations of keratinocyte proliferation, melanocyte density, smooth muscle hyperplasia and nerve fiber distribution in BN. Methods Clinical and pathological data were collected in 60 newly-diagnosed BN cases. Immunohistochemical stain of Ki-67, Melan-A, keratin 15, smooth muscle actin and protein gene product 9.5 was performed in 21 cases. Results The median diagnostic and onset age was 17 and 12 years, respectively. Skin lesions usually appeared on the upper trunk and upper limbs. The pathological features included the rete ridge elongation and fusion and basal hyperpigmentation. Epidermal Ki-67, Melan-A and keratin 15 expression and dermal nerve fiber length were significantly higher in lesional and perilesional skin than in normal skin (p<0.05~0.01), while smooth muscle actin expression was upregulated only in skin lesion (p<0.05). Conclusion Although the clinical diagnosis of BN is often straightforward, histopathology is helpful to differentiate from other pigmentary disorders. The hyperproliferation of keratinocytes, melanocytes, arrector pili muscle and dermal nerve fibers could be involved in the pathogenesis of BN. PMID:27904268

  15. Altered S-nitrosylation of p53 is responsible for impaired antioxidant response in skeletal muscle during aging

    PubMed Central

    Baldelli, Sara; Ciriolo, Maria Rosa

    2016-01-01

    p53 transcriptional activity has been proposed to regulate both homeostasis and sarcopenia of skeletal muscle during aging. However, the exact molecular function of p53 remains to be clearly defined. We demonstrated a requirement of nuclear p53 S-nitrosylation in inducing a nitric oxide/PGC-1α-mediated antioxidant pathway in skeletal muscle. Importantly, mutant form of p53-DNA binding domain (C124S) did not undergo nuclear S-nitrosylation and failed in inducing the expression of antioxidant genes (i.e. SOD2 and GCLC). Moreover, we found that during aging the nuclear S-nitrosylation of p53 significantly declines in gastrocnemius/soleus leading to an impairment of redox homeostasis of skeletal muscle. We suggested that decreased level of nuclear neuronal nitric oxide synthase (nNOS)/Syntrophin complex, which we observed during aging, could be responsible for impaired nuclear S-nitrosylation. Taken together, our data indicate that altered S-nitrosylation of p53 during aging could be a contributing factor of sarcopenia condition and of other skeletal muscle pathologies associated with oxidative/nitrosative stress. PMID:28025407

  16. Muscle Protein Alterations in LGMD2I Patients With Different Mutations in the Fukutin-related Protein Gene

    PubMed Central

    Yamamoto, Lydia U.; Velloso, Fernando J.; Lima, Bruno L.; Fogaça, Luciana L.Q.; de Paula, Flávia; Vieira, Natássia M.; Zatz, Mayana; Vainzof, Mariz

    2008-01-01

    Fukutin-related protein (FKRP) is a protein involved in the glycosylation of cell surface molecules. Pathogenic mutations in the FKRP gene cause both the more severe congenital muscular dystrophy Type 1C and the milder Limb-Girdle Type 2I form (LGMD2I). Here we report muscle histological alterations and the analysis of 11 muscle proteins: dystrophin, four sarcoglycans, calpain 3, dysferlin, telethonin, collagen VI, α-DG, and α2-laminin, in muscle biopsies from 13 unrelated LGMD2I patients with 10 different FKRP mutations. In all, a typical dystrophic pattern was observed. In eight patients, a high frequency of rimmed vacuoles was also found. A variable degree of α2-laminin deficiency was detected in 12 patients through immunofluorescence analysis, and 10 patients presented α-DG deficiency on sarcolemmal membranes. Additionally, through Western blot analysis, deficiency of calpain 3 and dystrophin bands was found in four and two patients, respectively. All the remaining proteins showed a similar pattern to normal controls. These results suggest that, in our population of LGMD2I patients, different mutations in the FKRP gene are associated with several secondary muscle protein reductions, and the deficiencies of α2-laminin and α-DG on sections are prevalent, independently of mutation type or clinical severity. (J Histochem Cytochem 56:995–1001, 2008) PMID:18645206

  17. Opposing roles of PIK3CA gene alterations to EZH2 signaling in non-muscle invasive bladder cancer.

    PubMed

    Segovia, Cristina; Martínez-Fernández, Mónica; Dueñas, Marta; Rubio, Carolina; López-Calderón, Fernando F; Costa, Clotilde; Saiz-Ladera, Cristina; Fernández-Grajera, María; Duarte, José; Muñoz, Huberto García; de la Rosa, Federico; Villacampa, Felipe; Castellano, Daniel; Paramio, Jesús M

    2017-02-07

    The high rates of tumor recurrence and progression represent a major clinical problem in non-muscle invasive bladder cancer. Previous data showed that EZH2-dependent signaling mediates these processes, whereas the frequent alterations of PIK3CA gene (copy gains and mutations) are predictive of reduced recurrence. Here we show, using clinical samples and bladder cancer cell lines, a functional interaction between EZH2- and PIK3CA-dependent signaling pathways. PIK3CA alterations mediated, on the one hand, the increased expression of two miRNAs, miR-101 and miR-138, which posttranscriptionally downregulate EZH2 expression. On the other hand, PIK3CA alterations facilitate the activation of Akt which phosphorylates EZH2 on Ser21, precluding the trimethylation of histone H3 in K27. Remarkably the increased expression of miR101 or miR138 and the expression of Ser21-phosphorylated EZH2 are good prognostic factors regarding non-muscle invasive bladder cancer recurrence and progression. Collectively, this study provides molecular evidences indicating that the gene expression rewiring occurring in primary bladder tumors, associated with increased EZH2 expression and activity and mediating the increased recurrence and progression risk, are prevented by PIK3CA-dependent signaling. This molecular process may have deep implications in the management of bladder cancer patients and in the design of novel molecularly targeted therapeutic approaches.

  18. Muscle cramp in Machado-Joseph disease: altered motor axonal excitability properties and mexiletine treatment.

    PubMed

    Kanai, Kazuaki; Kuwabara, Satoshi; Arai, Kimihito; Sung, Jia-Ying; Ogawara, Kazue; Hattori, Takamichi

    2003-04-01

    Machado-Joseph disease is one of the most common hereditary spinocerebellar degenerative disorders with a wide range of clinical manifestations. Pathology studies have shown mild to moderate loss of anterior horn cells and, in terms of spinal pathology, Machado-Joseph disease is regarded as a type of lower motoneuron disease. Muscle cramps are often associated with lower motoneuron disorders, but features of cramps in Machado-Joseph disease patients have never been studied. We investigated the incidence and nature of muscle cramps in Machado-Joseph disease patients, the excitability properties of motor axons [strength-duration time constant (tau(SD)), threshold electrotonus, refractoriness and supernormality] using threshold tracking and the effects of mexiletine hydrochloride on those cramps. Of 20 consecutive patients, 16 (80%) had frequent, severe muscle cramps in the legs, trunk or arms that disturbed their daily activities. The frequency of pathological muscle cramps was similar to that for patients with amyotrophic lateral sclerosis (68%) and higher than those for patients with spinal muscular atrophy (33%) or peripheral axonal neuropathy (24%). Threshold-tracking studies showed that tau(SD), which in part reflects Na(+) conductance at the resting membrane potential, was significantly greater in the Machado-Joseph disease patients than in normal subjects; severe muscle cramps were associated with a longer tau(SD). Threshold electrotonus, refractoriness and supernormality were not significantly different between Machado-Joseph disease patients and normal subjects. Eight Machado-Joseph disease patients with severe cramps, who received mexiletine treatment, experienced nearly complete relief with a partial normalization of tau(SD) (P = 0.08). Muscle cramps are a very frequent and disabling factor in Machado-Joseph disease. Pathological muscle cramps responded well to mexiletine treatment, and this is consistent with the hypothesis that they are caused by an

  19. Neuromuscular development in the absence of programmed cell death: phenotypic alteration of motoneurons and muscle.

    PubMed

    Buss, Robert R; Gould, Thomas W; Ma, Jianjun; Vinsant, Sharon; Prevette, David; Winseck, Adam; Toops, Kimberly A; Hammarback, James A; Smith, Thomas L; Oppenheim, Ronald W

    2006-12-27

    The widespread, massive loss of developing neurons in the central and peripheral nervous system of birds and mammals is generally considered to be an evolutionary adaptation. However, until recently, models for testing both the immediate and long-term consequences of preventing this normal cell loss have not been available. We have taken advantage of several methods for preventing neuronal death in vivo to ask whether rescued neurons [e.g., motoneurons (MNs)] differentiate normally and become functionally incorporated into the nervous system. Although many aspects of MN differentiation occurred normally after the prevention of cell death (including the expression of several motoneuron-specific markers, axon projections into the ventral root and peripheral nerves, ultrastructure, dendritic arborization, and afferent axosomatic synapses), other features of the neuromuscular system (MNs and muscle) were abnormal. The cell bodies and axons of MNs were smaller than normal, many MN axons failed to become myelinated or to form functional synaptic contacts with target muscles, and a subpopulation of rescued cells were transformed from alpha- to gamma-like MNs. Additionally, after the rescue of MNs in myogenin glial cell line-derived neurotrophic factor (MyoGDNF) transgenic mice, myofiber differentiation of extrafusal skeletal muscle was transformed and muscle physiology and motor behaviors were abnormal. In contrast, extrafusal myofiber phenotype, muscle physiology, and (except for muscle strength tests) motor behaviors were all normal after the rescue of MNs by genetic deletion of the proapoptotic gene Bax. However, there was an increase in intrafusal muscle fibers (spindles) in Bax knock-out versus both wild-type and MyoGDNF mice. Together, these data indicate that after the prevention of MN death, the neuromuscular system becomes transformed in novel ways to compensate for the presence of the thousands of excess cells.

  20. Altered Interleukin-10 Signaling in Skeletal Muscle Regulates Obesity-Mediated Inflammation and Insulin Resistance.

    PubMed

    Dagdeviren, Sezin; Jung, Dae Young; Lee, Eunjung; Friedline, Randall H; Noh, Hye Lim; Kim, Jong Hun; Patel, Payal R; Tsitsilianos, Nicholas; Tsitsilianos, Andrew V; Tran, Duy A; Tsougranis, George H; Kearns, Caitlyn C; Uong, Cecilia P; Kwon, Jung Yeon; Muller, Werner; Lee, Ki Won; Kim, Jason K

    2016-12-01

    Skeletal muscle insulin resistance is a major characteristic of obesity and type 2 diabetes. Although obesity-mediated inflammation is causally associated with insulin resistance, the underlying mechanism is unclear. Here, we examined the effects of chronic obesity in mice with muscle-specific overexpression of interleukin-10 (M(IL10)). After 16 weeks of a high-fat diet (HFD), M(IL10) mice became markedly obese but showed improved insulin action compared to that of wild-type mice, which was largely due to increased glucose metabolism and reduced inflammation in skeletal muscle. Since leptin regulates inflammation, the beneficial effects of interleukin-10 (IL-10) were further examined in leptin-deficient ob/ob mice. Muscle-specific overexpression of IL-10 in ob/ob mice (MCK-IL10(ob/ob)) did not affect spontaneous obesity, but MCK-IL10(ob/ob) mice showed increased glucose turnover compared to that in ob/ob mice. Last, mice with muscle-specific ablation of IL-10 receptor (M-IL10R(-/-)) were generated to determine whether IL-10 signaling in skeletal muscle is involved in IL-10 effects on glucose metabolism. After an HFD, M-IL10R(-/-) mice developed insulin resistance with reduced glucose metabolism compared to that in wild-type mice. Overall, these results demonstrate IL-10 effects to attenuate obesity-mediated inflammation and improve insulin sensitivity in skeletal muscle, and our findings implicate a potential therapeutic role of anti-inflammatory cytokines in treating insulin resistance and type 2 diabetes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  1. RBFOX1 Cooperates with MBNL1 to Control Splicing in Muscle, Including Events Altered in Myotonic Dystrophy Type 1

    PubMed Central

    Klinck, Roscoe; Fourrier, Angélique; Thibault, Philippe; Toutant, Johanne; Durand, Mathieu; Lapointe, Elvy; Caillet-Boudin, Marie-Laure; Sergeant, Nicolas; Gourdon, Geneviève; Meola, Giovanni; Furling, Denis; Puymirat, Jack; Chabot, Benoit

    2014-01-01

    With the goal of identifying splicing alterations in myotonic dystrophy 1 (DM1) tissues that may yield insights into targets or mechanisms, we have surveyed mis-splicing events in three systems using a RT-PCR screening and validation platform. First, a transgenic mouse model expressing CUG-repeats identified splicing alterations shared with other mouse models of DM1. Second, using cell cultures from human embryonic muscle, we noted that DM1-associated splicing alterations were significantly enriched in cytoskeleton (e.g. SORBS1, TACC2, TTN, ACTN1 and DMD) and channel (e.g. KCND3 and TRPM4) genes. Third, of the splicing alterations occurring in adult DM1 tissues, one produced a dominant negative variant of the splicing regulator RBFOX1. Notably, half of the splicing events controlled by MBNL1 were co-regulated by RBFOX1, and several events in this category were mis-spliced in DM1 tissues. Our results suggest that reduced RBFOX1 activity in DM1 tissues may amplify several of the splicing alterations caused by the deficiency in MBNL1. PMID:25211016

  2. Analysis by two-dimensional Blue Native/SDS-PAGE of membrane protein alterations in rat soleus muscle after hindlimb unloading.

    PubMed

    Basco, Davide; Nicchia, Grazia Paola; Desaphy, Jean-François; Camerino, Diana Conte; Frigeri, Antonio; Svelto, Maria

    2010-12-01

    Muscle atrophy occurring in several pathophysiological conditions determines decreases in muscle protein synthesis, increases in the rate of proteolysis and changes in muscle fiber composition. To determine the effect of muscle atrophy induced by hindlimb unloading (HU) on membrane proteins from rat soleus, a proteomic approach based on two-dimensional Blue Native/SDS-PAGE was performed. Proteomic analysis of normal and HU soleus muscle demonstrates statistically significant changes in the relative level of 36 proteins. Among the proteins identified by mass spectrometry, most are involved in pathways associated with muscle fuel utilization, indicating a shift in metabolism from oxidative to glycolytic. Moreover, immunoblotting analysis revealed an increase in aquaporin-4 (AQP4) water channel and an alteration of proteins belonging to the dystrophin-glycoprotein complex (DGC). AQP4 and DGC are regulated in soleus muscle subjected to simulated microgravity in response to compensatory mechanisms induced by muscle atrophy, and they parallel the slow-to-fast twitch conversion that occurs in soleus fibers during HU. In conclusion, the alterations of soleus muscle membrane proteome may play a pivotal role in the mechanisms involved in disuse-induced muscle atrophy.

  3. Healthy carbohydrates

    USDA-ARS?s Scientific Manuscript database

    Functional foods include dietary fiber consisting of health-promoting carbohydrates. We have produced novel prebiotics from orange peel and observed that they extend the shelf life of probiotic bacteria in synbiotics. Some pectic-oligosaccharides and xyloglucan-oligosaccharides also have anti-adhesi...

  4. A Four-Compartment Metabolomics Analysis of the Liver, Muscle, Serum, and Urine Response to Polytrauma with Hemorrhagic Shock following Carbohydrate Prefeed

    PubMed Central

    Witowski, Nancy; Lusczek, Elizabeth; Determan, Charles; Lexcen, Daniel; Mulier, Kristine; Ostrowski, Beverly; Beilman, Greg

    2015-01-01

    Objective Hemorrhagic shock accompanied by injury represents a major physiologic stress. Fasted animals are often used to study hemorrhagic shock (with injury). A fasted state is not guaranteed in the general human population. The objective of this study was to determine if fed animals would exhibit a different metabolic profile in response to hemorrhagic shock with trauma when compared to fasted animals. Methods Proton (1H) NMR spectroscopy was used to determine concentrations of metabolites from four different compartments (liver, muscle, serum, urine) taken at defined time points throughout shock/injury and resuscitation. PLS-DA was performed and VIP lists established for baseline, shock and resuscitation (10 metabolites for each compartment at each time interval) on metabolomics data from surviving animals. Results Fed status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The death rate for CPF animals is higher than FS animals (47 vs 28%). The majority of deaths occur post-resuscitation suggesting reperfusion injury. The metabolomics response to shock reflects priorities evident at baseline. FS animals raise the baseline degree of proteolysis to provide additional amino acids for energy production while CPF animals rely on both glucose and, to a lesser extent, amino acids. During early resuscitation levels of metabolites associated with energy production drop, suggesting diminished demand. Conclusions Feeding status prior to the occurrence of hemorrhagic shock with injury alters the metabolic course of this trauma and potentially affects mortality. The response to shock reflects metabolic priorities at baseline. PMID:25875111

  5. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle.

    PubMed

    Lee, Yang; Fluckey, James D; Chakraborty, Sanjukta; Muthuchamy, Mariappan

    2017-07-01

    Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility. LMCs were treated with different concentrations of insulin or glucose or both at various time points to determine insulin resistance. Onset of insulin resistance significantly impaired glucose uptake, mitochondrial function, oxygen consumption rates, glycolysis, lactic acid, and ATP production in LMCs. Hyperglycemia and hyperinsulinemia also impaired the PI3K/Akt while enhancing the ERK/p38MAPK/JNK pathways in LMCs. Increased NF-κB nuclear translocation and macrophage chemoattractant protein-1 and VCAM-1 levels in insulin-resistant LMCs indicated activation of inflammatory mechanisms. In addition, increased phosphorylation of myosin light chain-20, a key regulator of lymphatic muscle contraction, was observed in insulin-resistant LMCs. Therefore, our data elucidate the mechanisms of insulin resistance in LMCs and provide the first evidence that hyperglycemia and hyperinsulinemia promote insulin resistance and impair lymphatic contractile status by reducing glucose uptake, altering cellular metabolic pathways, and activating inflammatory signaling cascades.-Lee, Y., Fluckey, J. D., Chakraborty, S., Muthuchamy, M. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle. © FASEB.

  6. Endurance training alters skeletal muscle MCT contents in T2DM men.

    PubMed

    Opitz, D; Lenzen, E; Schiffer, T; Hermann, R; Hellmich, M; Bloch, W; Brixius, K; Brinkmann, C

    2014-12-01

    Patients suffering from type 2 diabetes mellitus (T2DM) often exhibit chronic elevated lactate levels which can promote peripheral insulin resistance by disturbing skeletal muscle insulin-signaling. Monocarboxylate transporter (MCT) proteins transfer lactate molecules through cellular membranes. MCT-1 and MCT-4 are the main protein isoforms expressed in human skeletal muscle, with MCT-1 showing a higher affinity (lower Km) for lactate than MCT-4. T2DM patients have reduced membranous MCT-1 proteins. Consequently, the lactate transport between muscle cells and the circulation as well as within an intracellular lactate shuttle, involving mitochondria (where lactate can be further metabolized), can be negatively affected. This study investigates whether moderate cycling endurance training (3 times per week for 3 months) can change skele-tal muscle MCT contents in T2DM men (n=8, years=56±9, body mass index (BMI)=32±4 kg/m(2)). Protein content analyses (immuno-histochemical stainings) were performed in bio-psies taken from the vastus lateralis muscle. Intracellular MCT-1 proteins were up-regulated (relative increase+89%), while intracellular MCT-4 contents were down-regulated (relative decrease - 41%) following endurance training. Sarcolemmal MCT-1 and MCT-4 did not change. The question of whether the training-induced up-regulation of intracellular MCT-1 leads to an improved lactate transport (and clearance) in T2DM patients requires further research.

  7. Assessing altered motor unit recruitment patterns in paretic muscles of stroke survivors using surface electromyography

    NASA Astrophysics Data System (ADS)

    Hu, Xiaogang; Suresh, Aneesha K.; Rymer, William Z.; Suresh, Nina L.

    2015-12-01

    Objective. The advancement of surface electromyogram (sEMG) recording and signal processing techniques has allowed us to characterize the recruitment properties of a substantial population of motor units (MUs) non-invasively. Here we seek to determine whether MU recruitment properties are modified in paretic muscles of hemispheric stroke survivors. Approach. Using an advanced EMG sensor array, we recorded sEMG during isometric contractions of the first dorsal interosseous muscle over a range of contraction levels, from 20% to 60% of maximum, in both paretic and contralateral muscles of stroke survivors. Using MU decomposition techniques, MU action potential amplitudes and recruitment thresholds were derived for simultaneously activated MUs in each isometric contraction. Main results. Our results show a significant disruption of recruitment organization in paretic muscles, in that the size principle describing recruitment rank order was materially distorted. MUs were recruited over a very narrow force range with increasing force output, generating a strong clustering effect, when referenced to recruitment force magnitude. Such disturbances in MU properties also correlated well with the impairment of voluntary force generation. Significance. Our findings provide direct evidence regarding MU recruitment modifications in paretic muscles of stroke survivors, and suggest that these modifications may contribute to weakness for voluntary contractions.

  8. Immune alterations, lipid peroxidation, and muscle damage following a hill race.

    PubMed

    Simpson, Richard J; Wilson, Martin R; Black, James R; Ross, James A; Whyte, Greg P; Guy, Keith; Florida-James, Geraint D

    2005-04-01

    Hill races usually include large downhill running sections, which can induce significant degrees of muscle damage in a field setting. This study examined the link between muscle damage, oxidative stress, and immune perturbations following a 7-km mountainous hill race with 457 m of ascent and 457 m of descent. Venous blood samples were taken from 7 club level runners before, immediately after, and 48 hrs postrace. Samples were analysed for total and differential leukocyte counts, markers of muscle damage (CK), lipid peroxidation (MDA), and acute phase proteins (CRP; fibrinogen; alpha-1-ACT). The total antioxidant status (TEAC) and plasma levels of the proinflammatory cytokines IL-6, IL-8, and TNF-alpha were also determined. Subjective pain reports, and plasma activities of CK, MDA, and circulatory monocytes reached peak values at 48 hrs postrace (p < 0.05). TEAC and the cytokine IL-8 increased immediately after the race (p < 0.05). Plasma TNF-alpha remained unchanged (p > 0.05). Despite the reports of muscle damage and soreness, no evidence of an acute phase response was observed (p > 0.05), which may be explained by the failure of the race to induce a plasma TNF-alpha response. Future studies should examine the link between muscle damage, oxidative stress, and the acute phase response following hill races of longer duration with larger eccentric components.

  9. Altered skeletal muscle mitochondrial biogenesis but improved endurance capacity in trained OPA1-deficient mice.

    PubMed

    Caffin, F; Prola, A; Piquereau, J; Novotova, M; David, D J; Garnier, A; Fortin, D; Alavi, M V; Veksler, V; Ventura-Clapier, R; Joubert, F

    2013-12-01

    The role of OPA1, a GTPase dynamin protein mainly involved in the fusion of inner mitochondrial membranes, has been studied in many cell types, but only a few studies have been conducted on adult differentiated tissues such as cardiac or skeletal muscle cells. Yet OPA1 is highly expressed in these cells, and could play different roles, especially in response to an environmental stress like exercise. Endurance exercise increases energy demand in skeletal muscle and repeated activity induces mitochondrial biogenesis and activation of fusion-fission cycles for the synthesis of new mitochondria. But currently no study has clearly shown a link between mitochondrial dynamics and biogenesis. Using a mouse model of haploinsufficiency for the Opa1 gene (Opa1(+/-)), we therefore studied the impact of OPA1 deficiency on the adaptation ability of fast skeletal muscles to endurance exercise training. Our results show that, surprisingly, Opa1(+/-) mice were able to perform the same physical activity as control mice. However, the adaptation strategies of both strains after training differed: while in control mice mitochondrial biogenesis was increased as expected, in Opa1(+/-) mice this process was blunted. Instead, training in Opa1(+/-) mice led to an increase in endurance capacity, and a specific adaptive response involving a metabolic remodelling towards enhanced fatty acid utilization. In conclusion, OPA1 appears necessary for the normal adaptive response and mitochondrial biogenesis of skeletal muscle to training. This work opens new perspectives on the role of mitochondrial dynamics in skeletal muscle cells and during adaptation to stress.

  10. Evidence for Altered Ca2+ Handling in Growth Associated Protein 43-Knockout Skeletal Muscle

    PubMed Central

    Caprara, Giusy A.; Morabito, Caterina; Perni, Stefano; Navarra, Riccardo; Guarnieri, Simone; Mariggiò, Maria A.

    2016-01-01

    Neuronal growth-associated protein 43 (GAP43) has crucial roles in the nervous system, and during development, regeneration after injury, and learning and memory. GAP43 is expressed in mouse skeletal muscle fibers and satellite cells, with suggested its involvement in intracellular Ca2+ handling. However, the physiological role of GAP43 in muscle remains unknown. Using a GAP43-knockout (GAP43−/−) mouse, we have defined the role of GAP43 in skeletal muscle. GAP43−/− mice showed low survival beyond weaning, reduced adult body weight, decreased muscle strength, and changed myofiber ultrastructure, with no significant differences in the expression of markers of satellite cell and myotube progression through the myogenic program. Thus, GAP43 expression is involved in timing of muscle maturation in-vivo. Intracellular Ca2+ measurements in-vitro in myotubes revealed GAP43 involvement in Ca2+ handling. In the absence of GAP43 expression, the spontaneous Ca2+ variations had greater amplitudes and higher frequency. In GAP43−/− myotubes, also the intracellular Ca2+ variations induced by the activation of dihydropyridine and ryanodine Ca2+ channels, resulted modified. These evidences suggested dysregulation of Ca2+ homeostasis. The emerging hypothesis indicates that GAP43 interacts with calmodulin to indirectly modulate the activities of dihydropyridine and ryanodine Ca2+ channels. This thus influences intracellular Ca2+ dynamics and its related intracellular patterns, from functional excitation-contraction coupling, to cell metabolism, and gene expression. PMID:27833566

  11. Embryonic-only arsenic exposure in killifish (Fundulus heteroclitus) reduces growth and alters muscle IGF levels one year later.

    PubMed

    Szymkowicz, Dana B; Sims, Kaleigh C; Castro, Noemi M; Bridges, William C; Bain, Lisa J

    2017-05-01

    Arsenic is a contaminant of drinking water and crops in many parts of the world. Epidemiological studies have shown that arsenic exposure is linked to decreased birth weight, weight gain, and proper skeletal muscle function. The goal of this study was to use killifish (Fundulus heteroclitus) as a model to determine the long-term effects of embryonic-only arsenic exposure on muscle growth and the insulin-like growth factor (IGF) pathway. Killifish embryos were exposed to 0, 50, 200 or 800ppb As(III) from fertilization until hatching. Juvenile fish were reared in clean water and muscle samples were collected at 16, 28, 40 and 52 weeks of age. There were significant reductions in condition factors, ranging from 12 to 17%, in the fish exposed to arsenic at 16, 28 and 40 weeks of age. However, by 52 weeks, no significant changes in condition factors were seen. Alterations in IGF-1R and IGF-1 levels were assessed as a potential mechanism by which growth was reduced. While there no changes in hepatic IGF-1 transcripts, skeletal muscle cells can also produce their own IGF-1 and/or alter IGF-1 receptor levels to help enhance growth. After a 200 and 800ppb embryonic exposure, fish grown in clean water for 16 weeks had IGF-1R transcripts that were 2.8-fold and 2-fold greater, respectively, than unexposed fish. Through 40 weeks of age, IGF1-R remained elevated in the 200ppb and 800ppb embryonic exposure groups by 1.8-3.9-fold, while at 52 weeks of age, IGF-1R levels were still significantly increased in the 800ppb exposure group. Skeletal muscle IGF-1 transcripts were also significantly increased by 1.9-5.1 fold through the 52 weeks of grow-out in clean by water in the 800ppb embryonic exposure group. Based on these results, embryonic arsenic exposure has long-term effects in that it reduces growth and increases both IGF-1 and IGF-1R levels in skeletal muscle even 1year after the exposure has ended. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Slow to fast alterations in skeletal muscle fibers caused by clenbuterol, a beta(2)-receptor agonist

    NASA Technical Reports Server (NTRS)

    Zeman, Richard J.; Ludemann, Robert; Easton, Thomas G.; Etlinger, Joseph D.

    1988-01-01

    The effects of a beta(2)-receptor agonist, clenbuterol, and a beta(2) antagonist, butoxamine, on the skeletal muscle fibers of rats were investigated. It was found that chronic treatment of rats with clenbuterol caused hypertrophy of histochemically identified fast-twitch, but not slow-twitch, fibers within the soleus, while in the extensor digitorum longus the mean areas of both fiber types were increased; in both muscles, the ratio of the number of fast-twitch to slow-twitch fibers was increased. In contrast, a treatment with butoxamine caused a reduction of the fast-twitch fiber size in both muscles, and the ratio of the fast-twitch to slow-twitch fibers was decreased.