PMID- 28177708 OWN - NLM STAT- MEDLINE DCOM- 20180411 LR - 20211204 IS - 1715-5320 (Electronic) IS - 1715-5312 (Linking) VI - 42 IP - 6 DP - 2017 Jun TI - The effect of caffeine on skeletal muscle anabolic signaling and hypertrophy. PG - 621-629 LID - 10.1139/apnm-2016-0547 [doi] AB - Caffeine is a widely consumed stimulant with the potential to enhance physical performance through multiple mechanisms. However, recent in vitro findings have suggested that caffeine may block skeletal muscle anabolic signaling through AMP-activated protein kinase (AMPK)-mediated inhibition of mechanistic target of rapamycin (mTOR) signaling pathway. This could negatively affect protein synthesis and the capacity for muscle growth. The primary purpose of this study was to assess the effect of caffeine on in vivo AMPK and mTOR pathway signaling, protein synthesis, and muscle growth. In cultured C2C12 muscle cells, physiological levels of caffeine failed to impact mTOR activation or myoblast proliferation or differentiation. We found that caffeine administration to mice did not significantly enhance the phosphorylation of AMPK or inhibit signaling proteins downstream of mTOR (p70S6k, S6, or 4EBP1) or protein synthesis after a bout of electrically stimulated contractions. Skeletal muscle-specific knockout of LKB1, the primary AMPK activator in skeletal muscle, on the other hand, eliminated AMPK activation by contractions and enhanced S6k, S6, and 4EBP1 activation before and after contractions. In rats, the addition of caffeine did not affect plantaris hypertrophy induced by the tenotomy of the gastrocnemius and soleus muscles. In conclusion, caffeine administration does not impair skeletal muscle load-induced mTOR signaling, protein synthesis, or muscle hypertrophy. FAU - Moore, Timothy M AU - Moore TM AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. FAU - Mortensen, Xavier M AU - Mortensen XM AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. FAU - Ashby, Conrad K AU - Ashby CK AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. FAU - Harris, Alexander M AU - Harris AM AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. FAU - Kump, Karson J AU - Kump KJ AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. FAU - Laird, David W AU - Laird DW AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. FAU - Adams, Aaron J AU - Adams AJ AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. FAU - Bray, Jeremy K AU - Bray JK AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. FAU - Chen, Ting AU - Chen T AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. FAU - Thomson, David M AU - Thomson DM AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. AD - Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA. LA - eng PT - Journal Article DEP - 20170126 PL - Canada TA - Appl Physiol Nutr Metab JT - Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme JID - 101264333 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Carrier Proteins) RN - 0 (Cell Cycle Proteins) RN - 0 (Eif4ebp1 protein, mouse) RN - 0 (Eif4ebp1 protein, rat) RN - 0 (Eukaryotic Initiation Factors) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Phosphoproteins) RN - 3G6A5W338E (Caffeine) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/antagonists & inhibitors/genetics/metabolism MH - Adaptor Proteins, Signal Transducing MH - Animals MH - Caffeine/*administration & dosage MH - Carrier Proteins/genetics/metabolism MH - Cell Cycle Proteins MH - Cell Differentiation/drug effects MH - Cell Line MH - Cell Proliferation/drug effects MH - Electric Stimulation MH - Eukaryotic Initiation Factors MH - Hypertrophy MH - Intracellular Signaling Peptides and Proteins MH - Mice MH - Muscle, Skeletal/*drug effects/*growth & development MH - Myoblasts/cytology/drug effects/metabolism MH - Phosphoproteins/genetics/metabolism MH - Phosphorylation MH - Protein Biosynthesis MH - Proto-Oncogene Proteins c-akt/genetics/metabolism MH - Rats MH - Ribosomal Protein S6 Kinases, 70-kDa/genetics/metabolism MH - *Signal Transduction MH - TOR Serine-Threonine Kinases/*genetics/metabolism OTO - NOTNLM OT - AMPK OT - LKB1 OT - caffeine OT - cafeine OT - contraction OT - hypertrophie du muscle squelettique OT - mTOR OT - skeletal muscle hypertrophy EDAT- 2017/02/09 06:00 MHDA- 2018/04/12 06:00 CRDT- 2017/02/09 06:00 PHST- 2017/02/09 06:00 [pubmed] PHST- 2018/04/12 06:00 [medline] PHST- 2017/02/09 06:00 [entrez] AID - 10.1139/apnm-2016-0547 [doi] PST - ppublish SO - Appl Physiol Nutr Metab. 2017 Jun;42(6):621-629. doi: 10.1139/apnm-2016-0547. Epub 2017 Jan 26.