Hypothalamic Endoplasmic Reticulum Stress Of Overtrained Mice After Recovery

knowing the relationship between endoplasmic reticulum (ER) stress and inflammation and based on the fact that downhill running-based overtraining (OT) model increases hypothalamus levels of some pro-inflammatory cytokines, we verified the effects of three OT protocols on the levels of BiP, pIRE-1 (Ser734), pPERK (Thr981), pelF2alpha (Ser52), ATF-6 and GRP-94 proteins in the mouse hypothalamus after two weeks of recovery. Methods: the mice were randomized into control (CT), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR) groups. After 2-week total recovery period (i.e., week 10), hypothalamus was removed and used for immunoblotting. Results: The OTR/down group exhibited high levels of BiP and ATF6. The other OT protocols showed higher levels of pPERK (Th981) and pelf-2alpha (Ser52) when compared with the CT group. Conclusion: The current results suggest that after a 2-week total recovery period, the overtrained groups increased partially their ER stress protein levels, but without hypothalamic inflammation, which characterizes a physiological condition related to an adaptation mechanism.2

Serum and plasma hormonal concentrations are sensitive to periods of intensity and volume of soccer training

Objectifs Évaluer les effets d’un programme d’entraînement de 12 semaines sur les concentrations hormonales et la performance physiologique des joueurs de football. Sujets et méthodes Dix-huit sujets ont été évalués au commencement (T1), au milieu (T2) et à la fin (T3) de la saison. Leur sang a été recueilli pour l’analyse du cortisol, testostérone, rapport testostérone/cortisol, épinéphrine et norépinéphrine. Les paramètres anaérobie lactique/alactique et le seuil anaérobie ont été utilisés comme mesures de performance physiologique. Résultats Tandis que les niveaux de cortisol étaient plus élevés en T2 et T3 comparés à ceux de T1 (p ≤ 0,05), les valeurs de testostérone et les rapports testostérone/cortisol étaient significativement moins élevés en T2 et T3 comparés à ceux de T1 (p ≤ 0,05). Les concentrations de norépinéphrine ont augmenté de T1 à T2 et T3 (p ≤ 0,05). En plus, alors qu’il y a eu une baisse significative des paramètres de la performance anaérobie alactique en T2 et T3 comparés à ceux de T1 (p ≤ 0,05), le seuil anaérobie s’est élevé en T2 et T3 comparé à T1 (p ≤ 0,05). En résumé, nous avons constaté que les niveaux de NE peuvent être utilisés comme marqueurs des variations de volume et intensité d’entraînement. En plus, les altérations dans les niveaux d’hormones sélectionnés dans cette étude n’ont pas été associées à des réponses négatives des performances physiologiques.Mots clés Cortisol; Testostérone; Testostérone/cortisol rapport; Catécholamines; Football

Aerobic And Anaerobic Performances In Tethered Swimming

The purpose of this study was to investigate whether the critical force (CritF) and anaerobic impulse capacity (AIC) - estimated by tethered swimming - reflect the aerobic and anaerobic performance of swimmers. 12 swimmers performed incremental test in tethered swimming to determine lactate anaerobic threshold (AnTLAC), maximal oxygen uptake (̇VO2MAX) and force associated with the ̇VO2MAX (i ̇VO2MAX). The swimmers performed 4 exhaustive (tlim) exercise bouts (100, 110, 120 and 130% i ̇VO2MAX) to compute the CritF and AIC (F vs. 1/tlim model); a 30-s all-out tethered swimming bout to determine their anaerobic fitness (ANF); 100, 200, and 400-m time-trials to determine the swimming performance. CritF (57.09±11.77 N) did not differ from AnTLAC (53.96±11.52 N, (P>0.05) but was significantly lower than i ̇VO2MAX (71.02±8.36 N). In addition, CritF presented significant correlation with AnTLAC (r=0.76; P<0.05) and i ̇VO2MAX (r=0.74; P<0.05). On the other hand, AIC (286.19±54.91 N.s) and ANF (116.10±13.66 N) were significantly correlated (r=0.81, p<0.05). In addition, CritF and AIC presented significant correlations with all time-trials. In summary, this study demonstrates that CritF and AIC can be used to evaluate AnTLAC and ANF and to predict 100, 200, and 400-m free swimming. © Georg Thieme Verlag KG Stuttgart . New York.348712719Almeida, A.G., Cunha, F.A.P., Rosa, M.R.R., Kokubun, E., Critical force in tethered swimming: Relationship with blood lactate and oxygen uptake (2004) Rev Bras Ciên Esporte, 24, pp. 47-59Billat, V.L., Morton, R.H., Blondel, N., Berthoin, S., Bocquet, V., Koralsztein, J.P., Barstow, T.J., Oxygen kinetics and modelling of time to exhaustion whilst running at various velocities at maximal oxygen uptake (2000) European Journal of Applied Physiology, 82 (3), pp. 178-187Bishop, D., Jenkins, D.G., The influence of resistance training on the critical power function and time to fatigue at critical power (1996) Aust J Sci Med Sport, 28, pp. 101-110Bland, J.M., Altman, D.G., Statistical methods for assessing agreement between two methods of clinical measurement (1986) Lancet, 1 (8476), pp. 307-310. , PII S0140673686908378Blondel, N., Berthoin, S., Billat, V., Lensel, G., Relationship between run times to exhaustion at 90, 100, 120, and 140% of vVO2max and velocity expressed relatively to critical velocity and maximal velocity (2001) International Journal of Sports Medicine, 22 (1), pp. 27-33. , DOI 10.1055/s-2001-11357Bonen, A., Wilson, B.A., Yarkony, M., Belcastro, A.N., Maximal oxygen uptake during free, tethered, and flume swimming (1980) Journal of Applied Physiology Respiratory Environmental and Exercise Physiology, 48 (2), pp. 232-235Bosquet, L., Delhors, P.R., Duchene, A., Dupont, G., Leger, L., Anaerobic running capacity determined from a 3-parameter systems model: Relationship with other anaerobic indices and with running performance in the 800 m-run (2007) International Journal of Sports Medicine, 28 (6), pp. 495-500. , DOI 10.1055/s-2006-924516Costill, D.L., Kovaleski, J., Porter, D., Energy expenditure during front crawl swimming: Predicting success in middle-distance events (1985) International Journal of Sports Medicine, 6 (5), pp. 266-270Dekerle, J., Brickley, G., Alberty, M., Pelayo, P., Characterising the slope of the distance-time relationship in swimming (2010) J Sci Med Sport, 13, pp. 365-370Dekerle, J., Brickley, G., Hammond, A.J.P., Pringle, J.S.M., Carter, H., Validity of the two-parameter model in estimating the anaerobic work capacity (2006) European Journal of Applied Physiology, 96 (3), pp. 257-264. , DOI 10.1007/s00421-005-0074-8Dekerle, J., Pelayo, P., Clipet, B., Depretz, S., Lefevre, T., Sidney, M., Critical swimming speed does not represent the speed at maximal lactate steady state (2005) International Journal of Sports Medicine, 26 (7), pp. 524-530. , DOI 10.1055/s-2004-821227Dekerle, J., Sidney, M., Hespel, J.M., Pelayo, P., Validity and reliability of critical speed, critical stroke rate, and anaerobic capacity in relation to front crawl swimming performances (2002) International Journal of Sports Medicine, 23 (2), pp. 93-98. , DOI 10.1055/s-2002-20125Di Prampero, P.E., Dekerle, J., Capelli, C., Zamparo, P., The critical velocity in swimming (2008) European Journal of Applied Physiology, 102 (2), pp. 165-171. , DOI 10.1007/s00421-007-0569-6Eckerson, J.M., Bull, A.A., Moore, G.A., Effect of thirty days of creatine supplementation with phosphate salts on anaerobic working capacity and body weight in men (2008) J Strength Cond Res, 22, pp. 826-832Ferguson, C., Whipp, B.J., Cathcart, A.J., Rossiter, H.B., Turner, A.P., Ward, S.A., Effects of prior very-heavy intensity exercise on indices of aerobic function and high-intensity exercise tolerance (2007) Journal of Applied Physiology, 103 (3), pp. 812-822. , http://jap.physiology.org/cgi/reprint/103/3/812, DOI 10.1152/japplphysiol.01410.2006Fernandes, R.J., Cardoso, C.S., Soares, S.M., Ascensao, A., Colaco, P.J., Vilas-Boas, J.P., Time Limit and VO2 Slow Component at Intensities Corresponding to VO2max in Swimmers (2003) International Journal of Sports Medicine, 24 (8), pp. 576-581. , DOI 10.1055/s-2003-43274Fernandes, R.J., Keskinen, K.L., Colaco, P., Querido, A.J., Machado, L.J., Morais, P.A., Novais, D.Q., Vilas Boas, J.P., Time limit at VO2max velocity in elite crawl swimmers (2008) International Journal of Sports Medicine, 29 (2), pp. 145-150. , DOI 10.1055/s-2007-965113Fukuba, Y., Miura, A., Endoi, M., Kan, A., Yanagawa, K., Whipp, B.J., The curvature constant parameter of the power-duration curve for varied-power exercise (2003) Medicine and Science in Sports and Exercise, 35 (8), pp. 1413-1418. , DOI 10.1249/01.MSS.0000079047.84364.70Green, S., Dawson, B.T., The Y-intercept of the maximal work-duration regression and field tests of anaerobic capacity in cyclists (1996) International Journal of Sports Medicine, 17 (1), pp. 41-47. , DOI 10.1055/s-2007-972806Harriss, D.J., Atkinson, G., Update - Ethical Standards in Sport and Exercise Science Research (2011) J Sports Med, 32, pp. 819-821Hill, D.W., Smith, J.C., A method to ensure the accuracy of estimates of anaerobic capacity derived using the critical power concept (1994) Journal of Sports Medicine and Physical Fitness, 34 (1), pp. 23-37Ikuta, Y., Wakayoshi, K., Nomura, T., Determination and validity of critical swimming force as performance index in tethered swimming (1996) Biomech Med Swimming, 7, pp. 146-151Jenkins, D.G., Quigley, B.M., The y-intercept of the critical power functions as a measure of anaerobic work capacity (1991) Ergonomics, 34, pp. 13-22Jones, A.M., Wilkerson, D.P., DiMenna, F., Fulford, J., Poole, D.C., Muscle metabolic responses to exercise above and below the "critical power" assessed using 31P-MRS (2008) American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 294 (2), pp. R585-R593. , http://ajpregu.physiology.org/cgi/reprint/294/2/R585, DOI 10.1152/ajpregu.00731.2007Jones, A.M., Vanhatal, A., Burnle, M., Morto, R.H., Poole, D.C., Critical Power: Implications for the determination of VO2 max and exercise tolerance (2010) Med Sci Sports Exerc, 42, pp. 1876-1890Kendall, K.L., Smith, A.E., Graef, J.L., Fukuda, D.H., Moon, J.R., Beck, T.W., Cramer, J.T., Stout, J.R., Effects of four weeks of high-intensity interval training and creatine supplementation on critical power and anaerobic working capacity in college-aged men (2009) J Strength Cond Res, 23, pp. 1663-1669Kuipers, H., Verstappen, F.T.J., Keizer, H.A., Variability of aerobic performance in the laboratory and its physiologic correlates (1985) International Journal of Sports Medicine, 6 (4), pp. 197-201Leclair, E., Borel, B., Thevenet, D., Baquet, G., Mucci, P., Berthoin, S., Assessment of child-specific aerobic fitness and anaerobic capacity by the use of the power-time relationships constants (2010) Pediatr Exerc Sci, 22, pp. 454-466Martin, R.B., Yeater, R.A., White, M.K., A simple analytical model for the crawl stroke (1981) Journal of Biomechanics, 14 (8), pp. 539-548. , DOI 10.1016/0021-9290(81)90003-8Matsumoto, I., Araki, H., Tsuda, K., Odajima, H., Nishima, S., Higaki, Y., Tanaka, H., Shindo, M., Effects of swimming training on aerobic capacity and exercise induced bronchoconstriction in children with bronchial asthma (1999) Thorax, 54 (3), pp. 196-201Miura, A., Endo, M., Sato, H., Sato, H., Barstow, T.J., Fukuba, Y., Relationship between the curvature constant parameter of the power-duration curve and muscle cross-sectional area of the thigh for cycle ergometry in humans (2002) European Journal of Applied Physiology, 87 (3), pp. 238-244. , DOI 10.1007/s00421-002-0623-3Monod, H., Scherrer, J., The work capacity of a synergic muscular group (1965) Ergonomics, 8, pp. 329-337Morouço, P., Keskinen, K.L., Vilas-Boas, J.P., Fernandes, R.J., Relationship between tethered forces and the four swimming techniques performance (2011) J Appl Biomech, 27, pp. 161-169Morton, R.H., The critical power and related whole-body bioenergetic models (2006) Eur J Appl Physiol, 96, pp. 339-354Papoti, M., Balikian, J.P., Denadai, B.S., Lima, M.C.S., Silva, A.S.R., Santhiago, V., Gobatto, C.A., Adaptation of the VO2000 gas analiser's mask to mensuration of cardiorespiratory parameters in swimming (2007) Rev Bras Med Esporte, 13, pp. 190-194Papoti, M., Martins, L.E.B., Cunha, S.A., Zagatto, A.M., Gobatto, C.A., Effects of taper on swimming force and Swimmer performance after an experimental ten-week training program (2007) Strength Cond Res, 21, pp. 538-542Papoti, M., Zagatto, A.M., Barbosa De Freitas Jr., P., Cunha, S.A., Barreto Martins, L.E., Gobatto, C.A., Use of the y-intercept in the evaluation of the anaerobic fitness and performance prediction of trained swimmers (2005) Revista Brasileira de Medicina do Esporte, 11 (2), pp. 126-130Perandini, L.A.B., Okuno, N.M., Kokubun, E., Nakamura, F.Y., Correlation between critical force and critical velocity and their respective stroke rates (2007) Rev Bras Cineantropom Desempenho Hum, 8, pp. 59-65Raglin, J.S., Koceja, D.M., Stager, J.M., Harms, C.A., Mood, neuromuscular function, and performance during training in female swimmers (1996) Medicine and Science in Sports and Exercise, 28 (3), pp. 372-377. , DOI 10.1097/00005768-199603000-00013Soares, S., Vilar, S., Bernardo, C., Campos, A., Fernandes, R., Vilas-Boas, J.P., Using data from the critical velocity regression line for the estimation of anaerobic capacity in infant and adult swimmers (2003) Portuguese J Sport Sci, 3, pp. 108-110Takahashi, S., Wakayoshi, K., Hayashi, A., Sakaguchi, Y., Kitagawa, K., A method for determining critical swimming velocity (2009) Int J Sports Med, 30, pp. 119-123Taylor, S.A., Batterham, A.M., The reproducibility of estimates of critical power and anaerobic work capacity in upper-body exercise (2002) European Journal of Applied Physiology, 87 (1), pp. 43-49. , DOI 10.1007/s00421-002-0586-4Toussaint, H.M., Wakayoshi, K., Hollander, A.P., Ogita, F., Simulated front crawl swimming performance related to critical speed and critical power (1998) Medicine and Science in Sports and Exercise, 30 (1), pp. 144-151. , DOI 10.1097/00005768-199801000-00020West, S.A., Drummond, M.J., VanNess, J.M., Ciccolella, M.E., 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Nonfunctional Overreaching Leads To Inflammation And Myostatin Upregulation In Swiss Mice

The aims of the this study were a) to verify whether the performance decrease induced by nonfunctional overreaching (NFOR) is linked to high concentrations of cytokines in serum, skeletal muscles and liver; b) to verify muscle myostatin adaptation to NFOR; c) to verify the effects of chronic glucose supplementation on the parameters mentioned above. Mice were divided into control (C), trained (TR), overtrained (OTR) and supplemented overtrained (OTR+S). The incremental load test (ILT) and exhaustive test (ET) were used to measure performances before and after exercise protocols. 24 h after ET, muscles and liver were removed and stored at -80°C for subsequent measurements. Total blood was collected from decapitation for subsequent determination of cytokine concentrations. Generally, OTR and OTR+S presented higher contents of IL-6, TNF-alpha, GLUT-4 and myostatin in muscle samples compared to C and TR. Glucose supplementation attenuated the high contents of IL-6, TNF-alpha and IL-15 in liver, and of IL-6 in serum. In summary, NFOR led to low-grade chronic inflammation and myostatin upregulation. © Georg Thieme Verlag KG Stuttgart · New York.352139146Adser, H., Wojtaszewski, J.F., Jakobsen, A.H., Kiilerich, K., Hidalgo, J., Pilegaard, H., Interleukin-6 modifies mRNA expression in mouse skeletal muscle (2011) Acta Physiol (Oxf), 202, pp. 165-173Allen, D.L., Hittel, D.S., McPherron, A.C., Expression and function of myostatin in obesity, diabetes, and exercise adaptation (2011) Med Sci Sports Exerc, 43, pp. 1828-1835Armstrong, R.B., Phelps, R.O., Muscle fiber type composition of the rat hindlimb (1984) American Journal of Anatomy, 171 (3), pp. 259-272. , DOI 10.1002/aja.1001710303Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254Carey, A.L., Steinberg, G.R., Macaulay, S.L., Thomas, W.G., Holmes, A.G., Ramm, G., Prelovsek, O., Febbraio, M.A., Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMP-activated protein kinase (2006) Diabetes, 55 (10), pp. 2688-2697. , http://diabetes.diabetesjournals.org/cgi/reprint/55/10/2688, DOI 10.2337/db05-1404Carmichael, M.D., Davis, J.M., Murphy, E.A., Carson, J.A., Van Rooijen, N., Mayer, E., Ghaffar, A., Role of brain macrophages on IL-1beta and fatigue following eccentric exercise-induced muscle damage (2010) Brain Behav Immun, 24, pp. 564-568Chen, T.C., Effects of a second bout of maximal eccentric exercise on muscle damage and electromyographic activity (2003) European Journal of Applied Physiology, 89 (2), pp. 115-121Chen, T.C., Hsieh, S.S., Effects of a 7-day eccentric training period on muscle damage and inflammation (2001) Medicine and Science in Sports and Exercise, 33 (10), pp. 1732-1738Costa, A., Dalloul, H., Hegyesi, H., Apor, P., Csende, Z., Racz, L., Vaczi, M., Tihanyi, J., Impact of repeated bouts of eccentric exercise on myogenic gene expression (2007) European Journal of Applied Physiology, 101 (4), pp. 427-436. , DOI 10.1007/s00421-007-0510-zDavis, J.M., Murphy, E.A., Carmichael, M.D., Zielinski, M.R., Groschwitz, C.M., Brown, A.S., Gangemi, J.D., Mayer, E.P., Curcumin effects on inflammation and performance recovery following eccentric exercise-induced muscle damage (2007) American Journal of Physiology - Regulatory Integrative and Comparative Physiology, 292 (6), pp. R2168-R2173. , http://ajpregu.physiology.org/cgi/reprint/292/6/R2168, DOI 10.1152/ajpregu.00858.2006Dubois, M., Gilles, K.A., Hamilton, J.K., Rebers, P.A., Smith, F., Colorimetric method for determination of sugar and related substances (1956) Anal Chem, 28, p. 6Ferreira, J.C.B., Rolim, N.P.L., Bartholomeu, J.B., Gobatto, C.A., Kokubun, E., Brum, P.C., Maximal lactate steady state in running mice: Effect of exercise training (2007) Clinical and Experimental Pharmacology and Physiology, 34 (8), pp. 760-765. , DOI 10.1111/j.1440-1681.2007.04635.xFujimoto, E., Machida, S., Higuchi, M., Tabata, I., Effects of nonexhaustive bouts of high-intensity intermittent swimming training on GLUT-4 expression in rat skeletal muscle (2010) J Physiol Sci, 60, pp. 95-101Halson, S.L., Jeukendrup, A.E., Does overtraining exist? An analysis of overreaching and overtraining research (2004) Sports Medicine, 34 (14), pp. 967-981. , DOI 10.2165/00007256-200434140-00003Harriss, D.J., Atkinson, G., Update - Ethical standards in sport and exercise science research (2011) Int J Sports Med, 32, pp. 819-821Hittel, D.S., Axelson, M., Sarna, N., Shearer, J., Huffman, K.M., Kraus, W.E., Myostatin decreases with aerobic exercise and associates with insulin resistance (2010) Med Sci Sports Exerc, 42, pp. 2023-2029Hohl, R., Ferraresso, R.L., De Oliveira, R.B., Lucco, R., Brenzikofer, R., De Macedo, D.V., Development and characterization of an overtraining animal model (2009) Med Sci Sports Exerc, 41, pp. 1155-1163Kawanishi, N., Yano, H., Mizokami, T., Takahashi, M., Oyanagi, E., Suzuki, K., Exercise training attenuates hepatic inflammation, fibrosis and macrophage infiltration during diet induced-obesity in mice (2012) Brain Behav Immun, 26, pp. 931-941Keller, C., Steensberg, A., Hansen, A.K., Fischer, C.P., Plomgaard, P., Pedersen, B.K., Effect of exercise, training, and glycogen availability on IL-6 receptor expression in human skeletal muscle (2005) Journal of Applied Physiology, 99 (6), pp. 2075-2079. , DOI 10.1152/japplphysiol.00590.2005Kelly, M., Gauthier, M.S., Saha, A.K., Ruderman, N.B., Activation of AMP-activated protein kinase by interleukin-6 in rat skeletal muscle: Association with changes in cAMP, energy state, and endogenous fuel mobilization (2009) Diabetes, 58, pp. 1953-1960Li, T.-L., Gleeson, M., The effect of single and repeated bouts of prolonged cycling on leukocyte redistribution, neutrophil degranulation, IL-6, and plasma stress hormone responses (2004) International Journal of Sport Nutrition and Exercise Metabolism, 14 (5), pp. 501-516Matsakas, A., Bozzo, C., Cacciani, N., Caliaro, F., Reggiani, C., Mascarello, F., Patruno, M., Effect of swimming on myostatin expression in white and red gastrocnemius muscle and in cardiac muscle of rats (2006) Experimental Physiology, 91 (6), pp. 983-994. , DOI 10.1113/expphysiol.2006.033571Meeusen, R., Nederhof, E., Buyse, L., Roelands, B., De Schutter, G., Piacentini, M.F., Diagnosing overtraining in athletes using the two-bout exercise protocol (2010) Br J Sports Med, 44, pp. 642-648Meier, P., Renga, M., Hoppeler, H., Baum, O., The impact of antioxidant supplements and endurance exercise on genes of the carbohydrate and lipid metabolism in skeletal muscle of mice (2012) Cell Biochem Funct, , 10.1002/cbf.2859Moon, M.K., Cho, B.J., Lee, Y.J., Choi, S.H., Lim, S., Park, K.S., Park, Y.J., Jang, H.C., The effects of chronic exercise on the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha are different with age (2012) Appl Physiol Nutr Metab, 37, pp. 631-636Nieman, D.C., Davis, J.M., Henson, D.A., Gross, S.J., Dumke, C.L., Utter, A.C., Vinci, D.M., Triplett, N.T., Muscle cytokine mRNA changes after 2.5 h of cycling: Influence of carbohydrate (2005) Medicine and Science in Sports and Exercise, 37 (8), pp. 1283-1290. , DOI 10.1249/01.mss.0000175054.99588.b1Nosaka, K., Newton, M., Repeated eccentric exercise bouts do not exacerbate muscle damage and repair (2002) J Strength Cond Res, 16, pp. 117-122Pedersen, B.K., Muscular interleukin-6 and its role as an energy sensor (2012) Med Sci Sports Exerc, 44, pp. 392-396Pedersen, B.K., Febbraio, M.A., Muscles, exercise and obesity: Skeletal muscle as a secretory organ (2012) Nat Rev Endocrinol, 8, pp. 457-465Pedersen, B.K.F.M., Muscle as an endocrine organ: Focus on muscle-derived interleukin-6 (2008) Physiol Rev, 88, p. 27Pederson, B.A., Cope, C.M., Schroeder, J.M., Smith, M.W., Irimia, J.M., Thurberg, B.L., DePaoli-Roach, A.A., Roach, P.J., Exercise capacity of mice genetically lacking muscle glycogen synthase: In mice, muscle glycogen is not essential for exercise (2005) Journal of Biological Chemistry, 280 (17), pp. 17260-17265. , DOI 10.1074/jbc.M410448200Pereira, B.C., Filho, L.A., Alves, G.F., Pauli, J.R., Ropelle, E.R., Souza, C.T., Cintra, D.E., Silva, A.S., A new overtraining protocol for mice based on downhill running sessions (2012) Clin Exp Pharmacol Physiol, 39, pp. 793-798Robson, P.J., Elucidating the unexplained underperformance syndrome in endurance athletes: The interleukin-6 hypothesis (2003) Sports Medicine, 33 (10), pp. 771-781. , DOI 10.2165/00007256-200333100-00004Ross, R., Atherosclerosis - An inflammatory disease (1999) New England Journal of Medicine, 340 (2), pp. 115-126. , DOI 10.1056/NEJM199901143400207Sano, A., Koshinaka, K., Abe, N., Morifuji, M., Koga, J., Kawasaki, E., Kawanaka, K., The effect of high-intensity intermittent swimming on post-exercise glycogen supercompensation in rat skeletal muscle (2012) J Physiol Sci, 62, pp. 1-9Smith, L.L., Cytokine hypothesis of overtraining: A physiological adaptation to excessive stress? 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Endurance Exercise Training Increases Appl1 Expression And Improves Insulin Signaling In The Hepatic Tissue Of Diet-induced Obese Mice, Independently Of Weight Loss

Hepatic insulin resistance is the major contributor to fasting hyperglycemia in type 2 diabetes. The protein kinase Akt plays a central role in the suppression of gluconeogenesis involving forkhead box O1 (Foxo1) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), and in the control of glycogen synthesis involving the glycogen synthase kinase beta (GSK3β) in the liver. It has been demonstrated that endosomal adaptor protein APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor, tribbles-related protein 3 (TRB3), improving the action of insulin in the liver. Here, we demonstrated that chronic exercise increased the basal levels and insulin-induced Akt serine phosphorylation in the liver of diet-induced obese mice. Endurance training was able to increase APPL1 expression and the interaction between APPL1 and Akt. Conversely, training reduced both TRB3 expression and TRB3 and Akt association. The positive effects of exercise on insulin action are reinforced by our findings that showed that trained mice presented an increase in Foxo1 phosphorylation and Foxo1/PGC-1α association, which was accompanied by a reduction in gluconeogenic gene expressions (PEPCK and G6Pase). Finally, exercised animals demonstrated increased at basal and insulin-induced GSK3β phosphorylation levels and glycogen content at 24h after the last session of exercise. 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Acute Exercise Decreases Ptp-1b Protein Level And Improves Insulin Signaling In The Liver Of Old Rats

It is now commonly accepted that chronic inflammation associated with obesity during aging induces insulin resistance in the liver. In the present study, we investigated whether the improvement in insulin sensitivity and insulin signaling, mediated by acute exercise, could be associated with modulation of protein-tyrosine phosphatase 1B (PTP-1B) in the liver of old rats. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45 min rest period. Sixteen hours after the exercise, the rats were sacrificed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the fat mass was increased in old rats. The reduction in glucose disappearance rate (Kitt) observed in aged rats was restored 16 h after exercise. Aging increased the content of PTP-1B and attenuated insulin signaling in the liver of rats, a phenomenon that was reversed by exercise. Aging rats also increased the IRβ/PTP-1B and IRS-1/PTP-1B association in the liver when compared with young rats. Conversely, in the liver of exercised old rats, IRβ/PTP-1B and IRS-1/PTP-1B association was markedly decreased. Moreover, in the hepatic tissue of old rats, the insulin signalling was decreased and PEPCK and G6Pase levels were increased when compared with young rats. Interestingly, 16 h after acute exercise, the PEPCK and G6Pase protein level were decreased in the old exercised group. 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