Conditional activation of akt in adult skeletal muscle induces rapid hypertrophy.
Skeletal muscle atrophy is a severe morbidity caused by a variety of conditions, including cachexia, cancer, AIDS, prolonged bedrest, and diabetes. One strategy in the treatment of atrophy is to induce the pathways normally leading to skeletal muscle hypertrophy. The pathways that are sufficient to induce hypertrophy in skeletal muscle have been the subject of some controversy. We describe here the use of a novel method to produce a transgenic mouse in which a constitutively active form of Akt can be inducibly expressed in adult skeletal muscle and thereby demonstrate that acute activation of Akt is sufficient to induce rapid and significant skeletal muscle hypertrophy in vivo, accompanied by activation of the downstream Akt/p70S6 kinase protein synthesis pathway. Upon induction of Akt in skeletal muscle, there was also a significant decrease in adipose tissue. These findings suggest that pharmacologic approaches directed toward activating Akt will be useful in inducing skeletal muscle hypertrophy and that an increase in lean muscle mass is sufficient to decrease fat storage.
Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Rd., Tarrytown, NY 10591-6707, USA.
Ka-Man V
KM
Lai
Michael
M
Gonzalez
William T
WT
Poueymirou
William O
WO
Kline
Erqian
E
Na
Elizabeth
E
Zlotchenko
Trevor N
TN
Stitt
Aris N
AN
Economides
George D
GD
Yancopoulos
David J
DJ
Glass
D000273:Adipose Tissue / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000818:Animals; D004789:Enzyme Activation; D005260:Female; D006984:Hypertrophy / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D013629:Tamoxifen / Q000494:pharmacology
D011518:Proto-Oncogene Proteins; D013629:Tamoxifen; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt