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MTor and exercise

Aiko Inoue, Xian Wu Cheng, Zhe Huang, Lina Hu, Ryosuke Kikuchi, Haiying Jiang, Limei Piao, Takeshi Sasaki, Kohji Itakura, Hongxian Wu, Guangxian Zhao, Yanna Lei, Guang Yang, Enbo Zhu, Xiang Li, Kohji Sato, Teruhiko Koike, Masafumi Kuzuya
BACKGROUND: Exercise train (ET) stimulates muscle response in pathological conditions, including aging. The molecular mechanisms by which exercise improves impaired adiponectin/adiponectin receptor 1 (AdipoR1)-related muscle actions associated with aging are poorly understood. Here we observed that in a senescence-accelerated mouse prone 10 (SAMP10) model, long-term ET modulated muscle-regenerative actions. METHODS: 25-week-old male SAMP10 mice were randomly assigned to the control and the ET (45 min/time, 3/week) groups for 4 months...
November 29, 2016: Journal of Cachexia, Sarcopenia and Muscle
Angelo M Taveira-DaSilva, Joel Moss
INTRODUCTION: Lymphangioleiomyomatosis (LAM) is a disease of women characterized by cystic lung destruction, lymphatic involvement, and renal angiomyolipomas. AREAS COVERED: LAM is caused by proliferation of abnormal smooth muscle-like LAM cells containing mutations and perhaps epigenetic modifications of the TSC1 or TSC2 genes, which encode, respectively, hamartin and tuberin, two proteins controlling the mechanistic target of rapamycin (mTOR) signaling pathway...
2016: Expert Opinion on Orphan Drugs
Barbara Kathage, Sebastian Gehlert, Anna Ulbricht, Laura Lüdecke, Victor E Tapia, Zacharias Orfanos, Daniela Wenzel, Wilhelm Bloch, Rudolf Volkmer, Bernd K Fleischmann, Dieter O Fürst, Jörg Höhfeld
The cochaperone BAG3 is a central protein homeostasis factor in mechanically strained mammalian cells. It mediates the degradation of unfolded and damaged forms of the actin-crosslinker filamin through chaperone-assisted selective autophagy (CASA). In addition, BAG3 stimulates filamin transcription in order to compensate autophagic disposal and to maintain the actin cytoskeleton under strain. Here we demonstrate that BAG3 coordinates protein synthesis and autophagy through spatial regulation of the mammalian target of rapamycin complex 1 (mTORC1)...
October 15, 2016: Biochimica et Biophysica Acta
Yu Kitaoka, Koichi Nakazato, Riki Ogasawara
Recent studies demonstrated that resistance exercise not only leads to muscle hypertrophy, but also improves mitochondrial function. Since it has been suggested that calorie restriction (CR) induces mitochondrial biogenesis, we examined the effects of resistance training with or without CR on muscle weight and key mitochondrial parameters in rat skeletal muscle. Four weeks of resistance training (thrice/week) increased gastrocnemius muscle weight in ad libitum-fed (AL) rats by 14%. The degree of muscle-weight increase by resistance training was lower in CR rats (7...
August 18, 2016: Journal of Applied Physiology
Ju Yong Bae, Ki Ok Shin, Jinhee Woo, Sang Heon Woo, Ki Soeng Jang, Yul Hyo Lee, Sunghwun Kang
PURPOSE: The purpose of this study was to investigate the effect of exercise and dietary change on obesity and insulin resistance and mTOR signaling protein levels in skeletal muscles of obese rats. METHODS: Sixty male Sprague-Dawley rats were divided into CO (Normal diet) and HF (High Fat diet) groups in order to induce obesity for 15 weeks. The rats were then subdivided into CO, COT (CO + Training), HF, HFT (HF + Training), HFND (Dietary change), and HFNDT (HFND + Training) groups (10 rats / group)...
June 2016: Journal of Exercise Nutrition & Biochemistry
Tong-Yan Liu, Xiao-Qing Xiong, Xing-Sheng Ren, Ming-Xia Zhao, Chang-Xiang Shi, Jue-Jin Wang, Ye-Bo Zhou, Feng Zhang, Ying Han, Xing-Ya Gao, Qi Chen, Yue-Hua Li, Yu-Ming Kang, Guo-Qing Zhu
Fibronectin type III domain-containing 5 (FNDC5) protein induces browning of subcutaneous fat, and mediates beneficial effects of exercise on metabolism. However, whether FNDC5 is associated with hepatic steatosis, autophagy, fatty acid oxidation (FAO) and lipogenesis remains unknown. Herein, we show the roles and mechanisms of FNDC5 in hepatic steatosis, autophagy and lipid metabolism. Fasted FNDC5(-/-) mice exhibited severe steatosis, reduced autophagy and FAO, and enhanced lipogenesis in liver compared with WT mice...
August 8, 2016: Diabetes
Riki Ogasawara, Satoshi Fujita, Troy A Hornberger, Yu Kitaoka, Yuhei Makanae, Koichi Nakazato, Ishii Naokata
Resistance exercise (RE) activates signalling by the mammalian target of rapamycin (mTOR), and it has been suggested that rapamycin-sensitive mTOR signalling controls RE-induced changes in protein synthesis, ribosome biogenesis, autophagy, and the expression of peroxisome proliferator gamma coactivator 1 alpha (PGC-1α). However, direct evidence to support the aforementioned relationships is lacking. Therefore, in this study, we investigated the role of rapamycin-sensitive mTOR in the RE-induced activation of muscle protein synthesis, ribosome biogenesis, PGC-1α expression and hypertrophy...
2016: Scientific Reports
Einar Eftestøl, Ingrid M Egner, Ida G Lunde, Stian Ellefsen, Tom Andersen, Cecilie Sjåland, Kristian Gundersen, Jo C Bruusgaard
It is often assumed that mechanical factors are important for effects of exercise on muscle, but during voluntary training and most experimental conditions the effects could solely be attributed to differences in electrical activity, and direct evidence for a mechanosensory pathway has been scarce. We here show that, in rat muscles stimulated in vivo under deep anesthesia with identical electrical activity patterns, isometric contractions induced twofold more hypertrophy than contractions with 50-60% of the isometric force...
October 1, 2016: American Journal of Physiology. Cell Physiology
Vassilios J Bezzerides, Colin Platt, Carolin Lerchenmüller, Kaavya Paruchuri, Nul Loren Oh, Chunyang Xiao, Yunshan Cao, Nina Mann, Bruce M Spiegelman, Anthony Rosenzweig
The mechanisms by which exercise mediates its multiple cardiac benefits are only partly understood. Prior comprehensive analyses of the cardiac transcriptional components and microRNAs dynamically regulated by exercise suggest that the CBP/p300-interacting protein CITED4 is a downstream effector in both networks. While CITED4 has documented functional consequences in neonatal cardiomyocytes in vitro, nothing is known about its effects in the adult heart. To investigate the impact of cardiac CITED4 expression in adult animals, we generated transgenic mice with regulated, cardiomyocyte-specific CITED4 expression...
June 16, 2016: JCI Insight
Jami M Gurley, Beth A Griesel, Ann Louise Olson
Exercise promotes glucose clearance by increasing skeletal muscle GLUT4-mediated glucose uptake. Importantly, exercise upregulates muscle GLUT4 expression in an insulin-independent manner under conditions of insulin resistance, such as with type 2 diabetes. However, the insulin-independent mechanism responsible for rescued muscle GLUT4 expression is poorly understood. We used voluntary wheel running (VWR) in mice to test the prevailing hypothesis that insulin-independent upregulation of skeletal muscle GLUT4 protein expression with exercise is through increased Glut4 transcription...
October 2016: Diabetes
Matthew H Sharp, Ryan P Lowery, C Brooks Mobley, Carlton D Fox, Eduardo O de Souza, Kevin A Shields, James C Healy, Ned Q Arick, Richard M Thompson, Michael D Roberts, Jacob M Wilson
OBJECTIVE: The purpose of this study was to investigate the effects of Fortetropin on skeletal muscle growth and strength in resistance-trained individuals and to investigate the anabolic and catabolic signaling effects using human and rodent models. METHODS: In the rodent model, male Wistar rats (250 g) were gavage fed with either 1.2 ml of tap water control (CTL) or 0.26 g Fortetropin for 8 days. Then rats participated in a unilateral plantarflexion exercise bout...
November 2016: Journal of the American College of Nutrition
David D Church, Neil A Schwarz, Mike B Spillane, Sarah K McKinley-Barnard, Tom L Andre, Alejandro J Ramirez, Darryn S Willoughby
OBJECTIVE: Ursolic acid administration following resistance exercise increases mammalian target of rapamycin complex 1 (mTORC1) activity and skeletal muscle IGF-1 concentration in murines in a manner similar to l-leucine yet remains unexamined in humans. This study examined serum and skeletal muscle insulin-like growth factor-1 (IGF-1) and Akt/mTORC1 signaling activity following ingestion of either ursolic acid or l-leucine immediately after resistance exercise. METHODS: Nine resistance-trained men performed 3 lower-body resistance exercise sessions involving 4 sets of 8-10 repetitions at 75%-80% one repetition maximum (1-RM) on the angled leg press and knee extension exercises...
June 22, 2016: Journal of the American College of Nutrition
Guillermo Escalante, Michelle Alencar, Bryan Haddock, Phillip Harvey
BACKGROUND: Phosphatidic acid (PA) is a lipid messenger that has been shown to increase muscle protein synthesis via signaling stimulation of the mammalian target of rapamycin (mTOR). MaxxTOR® (MT) is a supplement that contains PA as the main active ingredient but also contains other synergistic mTOR signaling substances including L-Leucine, Beta-Hydroxy-Beta-Methylbutyrate (HMB), and Vitamin D3. METHODS: Eighteen healthy strength-trained males were randomly assigned to a group that either consumed MT (n = 8, 22...
2016: Journal of the International Society of Sports Nutrition
Malte Puchert, Volker Adams, Axel Linke, Jürgen Engele
The chemokine CXCL12 and its primary receptor, CXCR4, not only promote developmental myogenesis, but also muscle regeneration. CXCL12 chemoattracts CXCR4-positive satellite cells/blood-borne progenitors to the injured muscle, promotes myoblast fusion, partially with existing myofibers, and induces angiogenesis in regenerating muscles. Interestingly, the mechanisms underlying muscle regeneration are in part identical to those involved in muscular adaptation to intensive physical exercise. These similarities now prompted us to determine whether physical exercise would impact the CXCL12 system in skeletal muscle...
September 2016: Cellular Signalling
Aleksandra Olow, Sabine Mueller, Xiaodong Yang, Rintaro Hashizume, Justin Meyerowitz, William Weiss, Adam C Resnick, Angela J Waanders, Lukas J A Stalpers, Mitchel S Berger, Nalin Gupta, C David James, Claudia K Petritsch, Daphne A Haas-Kogan
PURPOSE: Alteration of the BRAF/MEK/MAPK pathway is the hallmark of pediatric low-grade gliomas (PLGGs), and mTOR activation has been documented in the majority of these tumors. We investigated combinations of MEK1/2, BRAF(V600E) and mTOR inhibitors in gliomas carrying specific genetic alterations of the MAPK pathway. EXPERIMENTAL DESIGN: We used human glioma lines containing BRAF(V600E) (adult high-grade: AM-38, DBTRG, PLGG: BT40), or wild-type BRAF (pediatric high-grade: SF188, SF9427, SF8628) and isogenic systems of KIAA1549:BRAF-expressing NIH/3T3 cells and BRAF(V600E)-expressing murine brain cells...
November 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jin Hee Woo, Ki Ok Shin, Yul Hyo Lee, Ki Soeng Jang, Ju Yong Bae, Hee Tae Roh
[Purpose] The aim of this study was to investigate the effects of regular treadmill exercise on skeletal muscle Rictor-Akt and mTOR-Raptor-S6K1 signaling pathway in high-fat diet-induced obese mice. [Subjects and Methods] Four- week-old C57BL/6 mice were adopted and classified into normal diet group (ND, n = 10), normal diet and training group (NDT, n = 10), high-fat diet group (HF, n = 10), and high-fat diet and training group (HFT, n = 10). The exercise program consisted of a treadmill exercise provided at low intensity for 1-4 weeks, and moderate intensity for 5-8 weeks...
April 2016: Journal of Physical Therapy Science
Hiroyuki Kato, Kyoko Miura, Sayako Nakano, Katsuya Suzuki, Makoto Bannai, Yoshiko Inoue
Eccentric exercise results in prolonged muscle damage that may lead to muscle dysfunction. Although inflammation is essential to recover from muscle damage, excessive inflammation may also induce secondary damage, and should thus be suppressed. In this study, we investigated the effect of leucine-enriched essential amino acids on muscle inflammation and recovery after eccentric contraction. These amino acids are known to stimulate muscle protein synthesis via mammalian target of rapamycin (mTOR), which, is also considered to alleviate inflammation...
September 2016: Amino Acids
Zhi Xia, Jason Cholewa, Yan Zhao, Yue-Qin Yang, Hua-Yu Shang, Lucas Guimarães-Ferreira, Marshall Alan Naimo, Quan-Sheng Su, Nelo Eidy Zanchi
Several studies have indicated a positive influence of leucine supplementation and aerobic training on the aging skeletal muscle signaling pathways that control muscle protein balance and muscle remodeling. However, the effect of a combined intervention requires further clarification. Thirteen month old CD-1(®) mice were subjected to moderate aerobic exercise (45 min swimming per day with 3% body weight workload) and fed a chow diet with 5% leucine or 3.4% alanine for 8 weeks. Serum and plasma were prepared for glucose, urea nitrogen, insulin and amino acid profile analysis...
2016: Nutrients
Jackson J Fyfe, David J Bishop, Evelyn Zacharewicz, Aaron P Russell, Nigel K Stepto
We compared the effects of concurrent exercise, incorporating either high-intensity interval training (HIT) or moderate-intensity continuous training (MICT), on mechanistic target of rapamycin complex 1 (mTORC1) signaling and microRNA expression in skeletal muscle, relative to resistance exercise (RE) alone. Eight males (mean ± SD: age, 27 ± 4 yr; V̇o2 peak , 45.7 ± 9 ml·kg(-1)·min(-1)) performed three experimental trials in a randomized order: 1) RE (8 × 5 leg press repetitions at 80% 1-repetition maximum) performed alone and RE preceded by either 2) HIT cycling [10 × 2 min at 120% lactate threshold (LT); HIT + RE] or 3) work-matched MICT cycling (30 min at 80% LT; MICT + RE)...
June 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Tommy R Lundberg, Rodrigo Fernandez-Gonzalo, Per A Tesch, Eric Rullman, Thomas Gustafsson
Recent reports suggest that aerobic exercise may boost the hypertrophic response to short-term resistance training. This study explored the effects of an acute aerobic exercise bout on the transcriptional response to subsequent resistance exercise. Ten moderately trained men performed ∼45 min cycling on one leg followed by 4 × 7 maximal knee extensions for each leg, 15 min later. Thus, one limb performed aerobic and resistance exercise (AE + RE) while the opposing leg did resistance exercise only (RE). Biopsies were obtained from the vastus lateralis muscle of each leg 3 h after the resistance exercise bout...
June 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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