UNLABELLED: Administration of the mTORC1 inhibitor, rapamycin, to humans blocks the increase in skeletal muscle protein synthesis in response to resistance exercise or amino acid ingestion. OBJECTIVE: To determine whether rapamycin administration influences basal post-absorptive protein synthesis or breakdown in human skeletal muscle. MATERIALS/ METHODS:Six young (26±2 years) subjects were studied during two separate trials, in which each trial was divided into two consecutive 2 h basal periods. The trials were identical except during one trial a single oral dose (16 mg) of rapamycin was administered immediately prior to the second basal period. Muscle biopsies were obtained from the vastus lateralis at 0, 2, and 4 h to examine protein synthesis, mTORC1 signaling, and markers of autophagy (LC3B-I and LC3B-II protein) associated with each 2 h basal period. RESULTS: During the Control trial, muscle protein synthesis, whole body protein breakdown (phenylalanine Ra), mTORC1 signaling, and markers of autophagy were similar between both basal periods (p>0.05). During the Rapamycin trial, these variables were similar to the Control trial (p>0.05) and were unaltered by rapamycin administration (p>0.05). Thus, post-absorptive muscle protein metabolism and mTORC1 signaling were not affected by rapamycin administration. CONCLUSIONS: Short-term rapamycin administration may only impair protein synthesis in human skeletal muscle when combined with a stimulus such as resistance exercise or increased amino acid availability.
RCT Entities:
UNLABELLED: Administration of the mTORC1 inhibitor, rapamycin, to humans blocks the increase in skeletal muscle protein synthesis in response to resistance exercise or amino acid ingestion. OBJECTIVE: To determine whether rapamycin administration influences basal post-absorptive protein synthesis or breakdown in human skeletal muscle. MATERIALS/ METHODS: Six young (26±2 years) subjects were studied during two separate trials, in which each trial was divided into two consecutive 2 h basal periods. The trials were identical except during one trial a single oral dose (16 mg) of rapamycin was administered immediately prior to the second basal period. Muscle biopsies were obtained from the vastus lateralis at 0, 2, and 4 h to examine protein synthesis, mTORC1 signaling, and markers of autophagy (LC3B-I and LC3B-II protein) associated with each 2 h basal period. RESULTS: During the Control trial, muscle protein synthesis, whole body protein breakdown (phenylalanine Ra), mTORC1 signaling, and markers of autophagy were similar between both basal periods (p>0.05). During the Rapamycin trial, these variables were similar to the Control trial (p>0.05) and were unaltered by rapamycin administration (p>0.05). Thus, post-absorptive muscle protein metabolism and mTORC1 signaling were not affected by rapamycin administration. CONCLUSIONS: Short-term rapamycin administration may only impair protein synthesis in human skeletal muscle when combined with a stimulus such as resistance exercise or increased amino acid availability.
Authors: Hans C Dreyer; Satoshi Fujita; Jerson G Cadenas; David L Chinkes; Elena Volpi; Blake B Rasmussen Journal: J Physiol Date: 2006-07-27 Impact factor: 5.182
Authors: Beat Nyfeler; Philip Bergman; Ellen Triantafellow; Christopher J Wilson; Yanyi Zhu; Branko Radetich; Peter M Finan; Daniel J Klionsky; Leon O Murphy Journal: Mol Cell Biol Date: 2011-05-16 Impact factor: 4.272
Authors: Daniel J Klionsky; Hagai Abeliovich; Patrizia Agostinis; Devendra K Agrawal; Gjumrakch Aliev; David S Askew; Misuzu Baba; Eric H Baehrecke; Ben A Bahr; Andrea Ballabio; Bruce A Bamber; Diane C Bassham; Ettore Bergamini; Xiaoning Bi; Martine Biard-Piechaczyk; Janice S Blum; Dale E Bredesen; Jeffrey L Brodsky; John H Brumell; Ulf T Brunk; Wilfried Bursch; Nadine Camougrand; Eduardo Cebollero; Francesco Cecconi; Yingyu Chen; Lih-Shen Chin; Augustine Choi; Charleen T Chu; Jongkyeong Chung; Peter G H Clarke; Robert S B Clark; Steven G Clarke; Corinne Clavé; John L Cleveland; Patrice Codogno; María I Colombo; Ana Coto-Montes; James M Cregg; Ana Maria Cuervo; Jayanta Debnath; Francesca Demarchi; Patrick B Dennis; Phillip A Dennis; Vojo Deretic; Rodney J Devenish; Federica Di Sano; J Fred Dice; Marian Difiglia; Savithramma Dinesh-Kumar; Clark W Distelhorst; Mojgan Djavaheri-Mergny; Frank C Dorsey; Wulf Dröge; Michel Dron; William A Dunn; Michael Duszenko; N Tony Eissa; Zvulun Elazar; Audrey Esclatine; Eeva-Liisa Eskelinen; László Fésüs; Kim D Finley; José M Fuentes; Juan Fueyo; Kozo Fujisaki; Brigitte Galliot; Fen-Biao Gao; David A Gewirtz; Spencer B Gibson; Antje Gohla; Alfred L Goldberg; Ramon Gonzalez; Cristina González-Estévez; Sharon Gorski; Roberta A Gottlieb; Dieter Häussinger; You-Wen He; Kim Heidenreich; Joseph A Hill; Maria Høyer-Hansen; Xun Hu; Wei-Pang Huang; Akiko Iwasaki; Marja Jäättelä; William T Jackson; Xuejun Jiang; Shengkan Jin; Terje Johansen; Jae U Jung; Motoni Kadowaki; Chanhee Kang; Ameeta Kelekar; David H Kessel; Jan A K W Kiel; Hong Pyo Kim; Adi Kimchi; Timothy J Kinsella; Kirill Kiselyov; Katsuhiko Kitamoto; Erwin Knecht; Masaaki Komatsu; Eiki Kominami; Seiji Kondo; Attila L Kovács; Guido Kroemer; Chia-Yi Kuan; Rakesh Kumar; Mondira Kundu; Jacques Landry; Marianne Laporte; Weidong Le; Huan-Yao Lei; Michael J Lenardo; Beth Levine; Andrew Lieberman; Kah-Leong Lim; Fu-Cheng Lin; Willisa Liou; Leroy F Liu; Gabriel Lopez-Berestein; Carlos López-Otín; Bo Lu; Kay F Macleod; Walter Malorni; Wim Martinet; Ken Matsuoka; Josef Mautner; Alfred J Meijer; Alicia Meléndez; Paul Michels; Giovanni Miotto; Wilhelm P Mistiaen; Noboru Mizushima; Baharia Mograbi; Iryna Monastyrska; Michael N Moore; Paula I Moreira; Yuji Moriyasu; Tomasz Motyl; Christian Münz; Leon O Murphy; Naweed I Naqvi; Thomas P Neufeld; Ichizo Nishino; Ralph A Nixon; Takeshi Noda; Bernd Nürnberg; Michinaga Ogawa; Nancy L Oleinick; Laura J Olsen; Bulent Ozpolat; Shoshana Paglin; Glen E Palmer; Issidora Papassideri; Miles Parkes; David H Perlmutter; George Perry; Mauro Piacentini; Ronit Pinkas-Kramarski; Mark Prescott; Tassula Proikas-Cezanne; Nina Raben; Abdelhaq Rami; Fulvio Reggiori; Bärbel Rohrer; David C Rubinsztein; Kevin M Ryan; Junichi Sadoshima; Hiroshi Sakagami; Yasuyoshi Sakai; Marco Sandri; Chihiro Sasakawa; Miklós Sass; Claudio Schneider; Per O Seglen; Oleksandr Seleverstov; Jeffrey Settleman; John J Shacka; Irving M Shapiro; Andrei Sibirny; Elaine C M Silva-Zacarin; Hans-Uwe Simon; Cristiano Simone; Anne Simonsen; Mark A Smith; Katharina Spanel-Borowski; Vickram Srinivas; Meredith Steeves; Harald Stenmark; Per E Stromhaug; Carlos S Subauste; Seiichiro Sugimoto; David Sulzer; Toshihiko Suzuki; Michele S Swanson; Ira Tabas; Fumihiko Takeshita; Nicholas J Talbot; Zsolt Tallóczy; Keiji Tanaka; Kozo Tanaka; Isei Tanida; Graham S Taylor; J Paul Taylor; Alexei Terman; Gianluca Tettamanti; Craig B Thompson; Michael Thumm; Aviva M Tolkovsky; Sharon A Tooze; Ray Truant; Lesya V Tumanovska; Yasuo Uchiyama; Takashi Ueno; Néstor L Uzcátegui; Ida van der Klei; Eva C Vaquero; Tibor Vellai; Michael W Vogel; Hong-Gang Wang; Paul Webster; John W Wiley; Zhijun Xi; Gutian Xiao; Joachim Yahalom; Jin-Ming Yang; George Yap; Xiao-Ming Yin; Tamotsu Yoshimori; Li Yu; Zhenyu Yue; Michisuke Yuzaki; Olga Zabirnyk; Xiaoxiang Zheng; Xiongwei Zhu; Russell L Deter Journal: Autophagy Date: 2007-11-21 Impact factor: 16.016
Authors: Nathan Hodson; Daniel W D West; Andrew Philp; Nicholas A Burd; Daniel R Moore Journal: Am J Physiol Cell Physiol Date: 2019-08-28 Impact factor: 4.249
Authors: Dillon K Walker; John J Thaden; Agata Wierzchowska-McNew; Marielle P K J Engelen; Nicolaas E P Deutz Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2016-11-09 Impact factor: 3.205
Authors: Paul T Reidy; Michael S Borack; Melissa M Markofski; Jared M Dickinson; Christopher S Fry; Rachel R Deer; Elena Volpi; Blake B Rasmussen Journal: Eur J Appl Physiol Date: 2017-03-09 Impact factor: 3.078
Authors: Melissa M Markofski; Jared M Dickinson; Micah J Drummond; Christopher S Fry; Satoshi Fujita; David M Gundermann; Erin L Glynn; Kristofer Jennings; Douglas Paddon-Jones; Paul T Reidy; Melinda Sheffield-Moore; Kyle L Timmerman; Blake B Rasmussen; Elena Volpi Journal: Exp Gerontol Date: 2015-02-28 Impact factor: 4.032
Authors: David M Gundermann; Dillon K Walker; Paul T Reidy; Michael S Borack; Jared M Dickinson; Elena Volpi; Blake B Rasmussen Journal: Am J Physiol Endocrinol Metab Date: 2014-04-01 Impact factor: 4.310
Authors: Richie D Barclay; Joseph W Beals; Jenny Drnevich; Brian S Imai; Peter M Yau; Alexander V Ulanov; Neale A Tillin; Martha Villegas-Montes; Scott A Paluska; Peter W Watt; Michael De Lisio; Nicholas A Burd; Richard W Mackenzie Journal: Metabolism Date: 2019-10-31 Impact factor: 8.694
Authors: Andrew Philp; Simon Schenk; Joaquin Perez-Schindler; D Lee Hamilton; Leigh Breen; Erin Laverone; Stewart Jeromson; Stuart M Phillips; Keith Baar Journal: J Physiol Date: 2015-09-15 Impact factor: 5.182
Authors: Emily E Howard; Lee M Margolis; Claire E Berryman; Harris R Lieberman; J Philip Karl; Andrew J Young; Monty A Montano; William J Evans; Nancy R Rodriguez; Neil M Johannsen; Kishore M Gadde; Melissa N Harris; Jennifer C Rood; Stefan M Pasiakos Journal: Am J Physiol Endocrinol Metab Date: 2020-08-10 Impact factor: 4.310