The effect of caffeine on skeletal muscle anabolic signaling and hypertrophy.
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.
Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.|Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.
Timothy M
TM
Moore
Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.|Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.
Xavier M
XM
Mortensen
Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.|Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.
Conrad K
CK
Ashby
Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.|Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.
Alexander M
AM
Harris
Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.|Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.
Karson J
KJ
Kump
Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.|Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.
David W
DW
Laird
Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.|Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.
Aaron J
AJ
Adams
Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.|Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.
Jeremy K
JK
Bray
Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.|Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.
Ting
T
Chen
Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.|Department of Physiology and Developmental Biology, 4005 LSB, Brigham Young University, Provo, UT 84602, USA.
David M
DM
Thomson
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002110:Caffeine / Q000008:administration & dosage*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004558:Electric Stimulation; D039642:Eukaryotic Initiation Factors; D006984:Hypertrophy; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000254:growth & development*; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C499527:Eif4ebp1 protein, mouse; C499526:Eif4ebp1 protein, rat; D039642:Eukaryotic Initiation Factors; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D002110:Caffeine; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
AMPK; LKB1; caffeine; caféine; contraction; hypertrophie du muscle squelettique; mTOR; skeletal muscle hypertrophy