Official Journal of the American College of Sports Medicine exercise (baseline) and one-hour following the bout of resistance exercise. Muscle tissue samples were analyzed for phosphorylated levels of mTOR, p70S6K, and 4E- BP1 proteins. rEsuLTs: One-hour following the resistance exercise bout there were no differences between phosphorylated levels of mTOR or 4E-BP1 in Vbx or RT (p>0.05). Levels of phosphorylated p70S6K were increased at the one-hour post-exercise time-point in both Vbx (22±9 fold increase, p
<strong>Thursday</strong>, May 30, 2013 S232 Vol. 45 No. 5 Supplement (RR vs. RX/XX) had different methylation pattern following five weeks of training in both exercise protocols. AE+RE, 8,981 CpG sites (5952 genes), and RE, 3,432 CpG sites (2550 genes) had different methylation pattern between the 2 genotype groups. CONCLusION: As hypothesized, ACTN3 R577X genotype has a significant effect on the methylation profile in skeletal muscle at baseline and following five weeks of exercise training. Our findings suggest that ACTN3 R577X genotype can influence epigenetic signature and skeletal muscle response to exercise. This work was supported in part by the National Space Biology Research Institute NSBRI, NCC 9-58-70, MA01601 (Adams), UL1TR000153, and by NICHD/NINDS 5R24HD050846-08: NCMRR-DC Core Molecular and Functional Outcome Measures in Rehabilitation Medicine. 1216 Board #161 May 30, 9:00 AM - 10:30 AM Exercise Increases Insulin sensitivity related To Obesity By reducing The Pro-Inflammatory Biomarkers In rat skeletal Muscle Leandro P. Moura1 , Luciana S. Pauli2 , Eduardo R. Ropelle2 , Dennys E. Cintra2 , Rodolfo Marinho1 , Eliete Luciano1 , Maria Alice R. Mello1 , José Rodrigo Pauli2 . 1UNESP, São Paulo State University, Rio Claro, Brazil. 2Campinas University State, Limeira, Brazil. (No relationships reported) INTrOduCTION: Among non-pharmacological therapies for the treatment of Diabetes Mellitus stands out the regular practice of physical exercises. PurPOsE: The present study investigated the effects of physical exercise on proinflammatory proteins and insulin signaling in skeletal muscle of obese rats. METhOds: In order to analyze the effects of administration of high fat diet, young Wistar rats (1 month old) were divided into 3 groups: control (C) rats treated with standard chow and Sedentary (SO) and Trained Obese (TO) were fed with high fat diet during 8 weeks. The TO group was submitted to two sessions of 1 hour of swimming exercise with 30 min interval between them. The body weight, epididymal fat, insulin sensitivity (Kitt), glucose and insulin were measured. In skeletal muscle (gastrocnemius) the activity of the insulin signaling pathway such as analysis of insulin receptor (IR), insulin receptor substrate 1 (IRS-1) and protein kinase B (Akt) were analyzed. It was also analyzed in the gastrocnemius muscle expression of proinflammatory proteins such as Jun N-terminal kinase (JNK), IKappa kinase beta (IKKβ) and Toll Like Receptor (TLR-4). rEsuLTs: The results show that acute exercise did not alter the body weight of this animals, but was effective in decreasing the inflammatory process in obesity and improve insulin sensitivity by improving the activity of key proteins of the signaling cascade via this hormone. CONCLusION: It is concluded that acute exercise can reduce the inflammation induced by obesity regardless of body mass reduction. 1217 Board #162 May 30, 9:00 AM - 10:30 AM acute Normobaric hypoxia Blunts The Blood Glucose Peak after a high-glycemic Meal In humans Gommaar D’Hulst, Ruud Van Thienen, Peter Hespel, Louise Deldicque. KU Leuven, Leuven, Belgium. (No relationships reported) In muscle cells glucose transport is regulated by insulin and by stimuli that increase the demand for glucose such as contraction and hypoxia. Those latter stimuli are known to induce the translocation of GLUT4 vesicles from the cytoplasm to the cell membrane via, amongst others, the activation of PKB and/or AMPK. Unlike for insulin and contraction, much less is known about how hypoxia regulates glucose metabolism and induces GLUT4 translocation in human skeletal muscle. PurPOsE: To investigate the molecular mechanisms by which hypoxia regulates glucose transport in human skeletal muscle. METhOds: According to a randomized cross-over study, 15 healthy men participated in 2 experimental sessions separated by a 4-week wash-out period. After a standardized, high glycemic breakfast (65% carbohydrate, 29% fat and 6% protein, glycemic load: 56g), subjects were subjected in random order to either 4 hours of normoxia (NOR) or severe hypoxia (11% O2, HYP). Biopsies were taken at the start (T0), after 1h (T60) and at the end of the trial (T240). Arterial blood saturation (SpO2) was measured by pulsoximetry. Phosphorylation status and mRNA level of various molecular regulators involved in glucose metabolism were measured by Western Blot and qPCR, respectively. rEsuLTs: Mean SpO2 dropped from 99.0 ± 0.2% in NOR to 75.0 ± 2.0% in HYP. Blood glucose peaked ~60min after termination of breakfast in both NOR and HYP, but the peak was more pronounced in NOR (after 30min: NOR, 113.8 ± 5.4 mg.dl-1 vs. HYP, 102.2 ± 4.7 mg.dl-1, p < 0.10; after 60 min: NOR, 113.8 ± 5.4 vs. HYP, 89.5 ± 4.7 mg.dl-1, p < 0.05; after 90 min; NOR, 97.2 ± 3.7 vs. HYP, 85.6 ± 4.8 mg.dl-1, p < 0.05). There were no differences between conditions in plasma insulin at T0 and T60. In contrast, at T240, when blood glucose had returned to baseline levels, plasma insulin was ~2-fold higher in HYP compared to NOR (p < 0.05). Phospho-PKB (Ser473) followed the insulin pattern almost completely, with no differences between MEDICINE & SCIENCE IN SPORTS & EXERCISE ® conditions at T0 and T60, and a ~2-fold higher phosphorylation in HYP at T240 (p < 0.05). Phospho-AMPK (Thr172) and HIF-1α at protein or mRNA level did not differ between conditions or with time. CONCLusIONs: Acute systemic hypoxia rapidly blunts the peak in blood glucose after a high glycemic meal independently of plasma insulin concentrations and PKB and AMPK phosphorylation. 1218 Board #163 May 30, 9:00 AM - 10:30 AM autophagy In Muscle Of Mice during Exercise In a Fasted Or In a Fed state Marc Francaux, Damien Naslain, Hélène Gilson, Cécile Jamart. Université catholique de Louvain, Louvain-la-Neuve, Belgium. (No relationships reported) PurPOsE: Recent findings suggest that activation of autophagy in skeletal muscle is essential for inducing beneficial effects of exercise in mice fed with a high fat diet (He et al. Nature 481 :511-5, 2012). As autophagy is also activated by food deprivation and as exercising in a fasted state is a common practice in endurance athletes, we designed a study the purpose of which was investigating various markers of autophagy in skeletal muscle of mice running in a fasted or fed state. METhOds: Thirty-six C57BL6/R3 female mice, 12 weeks old, were divided into 4 groups. Eight animals were fed ad-libitum (NE-Fed) and 8 others were kept fasted (NE-Fasted) for 9h30 before being anesthetized and then sacrificed. The 16 other mice were submitted to an exercise of 1H30 on a treadmill at a speed of 10m/min, which corresponds to moderate intensity exercise for those mice. Half of the mice performed the exercise in a fasted state (Ex-Fasted) and the other half was fed ad libitum (Ex-Fed). Mice were anesthetized immediately after exercise completion and the gastrocnemius muscles were removed. Soluble proteins were extracted for Western blotting analyses. Plasma insulin concentration was assayed by ELISA. An ANOVA design was used to assess the statistical significance of the differences between the means. When appropriate, a Bonferroni test was applied as a post-hoc. rEsuLTs: As expected, fasting and exercise lowered plasma insulin concentration, which was the lowest in Ex-Fasted. The highest values of LC3b-II, ATG12 and GABARAP-I and the lowest value of p62 were observed in Ex-Fasted indicating that autophagy is more activated in this condition than in Ex-Fed and in NE-Fasted. The phosphorylation state of Ulk-1 (ser757) that controls the initiation of autophagy was also more decreased in EX-Fasted in comparison with the other conditions. Ulk-1 is controlled by mTORC1 whose activity was decreased as assessed by the phosphorylation state of two downstream targets (S6K1 and 4EBP1). mTORC1 is under the control of both AMPK and PKB. AMPK was unaffected in all conditions whereas PKB followed the changes observed in plasma insulin concentrations. CONCLusION: Exercising in a fasted state is an efficient strategy to activate autophagy in mice. This activation seems related to the decrease in plasma insulin concentration. 1219 Board #164 May 30, 9:00 AM - 10:30 AM Cachectic skeletal Muscle response To a Novel Bout Of Low Frequency stimulation Melissa Puppa, James Carson, FACSM. University of South Carolina, Columbia, SC. (No relationships reported) Cachexia is a condition of skeletal muscle wasting associated with an underlying disease. It is commonly associated with a loss in muscle function. While we have demonstrated exercise training benefits related to cachexia-induced muscle and body weight loss, the cachectic muscle’s response to an acute bout of exercise is unknown. PurPOsE: The purpose of this study was to determine if cachectic mice are able to respond to an acute bout of low frequency muscle stimulation (LoFS). METhOds: Cachectic ApcMin/+ (Min) and wild type (WT) mice had the left leg undergo a simulated endurance exercise bout, while the right leg served as the intraanimal control. The siatic nerve was stimulated for one second at 10Hz every other second for thirty minutes. Mice were sacrificed 3h after completion of the protocol. rEsuLTs: Min mice exhibited a 13.8±2.9% decrease in body weight from peak weight and gastrocnemius muscle mass was significantly reduced compared to WT mice (p
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