title: Akt deficiency attenuates muscle size and function but not the response to ActRIIB inhibition.
abstract: BACKGROUND
  Akt is a critical mediator of developmental skeletal muscle growth. Treatment with a soluble ActRIIB fusion protein (ActRIIB-mFc) increases skeletal muscle mass and strength by inhibiting myostatin and related peptides. Recent in vitro studies have suggested that Akt signaling is necessary for the ability of ActRIIB inhibition to induce muscle hypertrophy. Thus, we hypothesized that mice deficient in either Akt1 or Akt2 would not respond to in vivo inhibition of ActRIIB with ActRIIB-mFc treatment.
  
  
  RESULTS
  We analyzed body composition and muscle parameters in wild-type C57BL/6J and Akt1 and Akt2 knockout mice, and compared the responses to blockade of ActRIIB signaling via ActRIIB-mFc treatment. Mice lacking Akt1 or Akt2 had reduced muscle mass, grip strength and contractile force. However, deficiency of Akt1 or Akt2 did not prevent the ability of ActRIIB-mFc treatment to induce muscle hypertrophy, or increase grip strength and contractile force. Akt1 and Akt2 deficient mice responded similarly as wild type mice to ActRIIB-mFc treatment by increasing fiber size.
  
  
  CONCLUSIONS
  Akt1 and Akt2 are important for the regulation of skeletal muscle mass and function. However, these Akt isoforms are not essential for the ability of ActRIIB inhibition to regulate muscle size, fiber type, strength or contractile force.
authors.affiliation: Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Goncalves
authors.forename: Emidio E
authors.initials: EE
authors.lastname: Pistilli
authors.forename: Anthony
authors.initials: A
authors.lastname: Balduzzi
authors.forename: Morris J
authors.initials: MJ
authors.lastname: Birnbaum
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lachey
authors.forename: Tejvir S
authors.initials: TS
authors.lastname: Khurana
authors.forename: Rexford S
authors.initials: RS
authors.lastname: Ahima
mesh_terms: D030301:Activin Receptors, Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism*; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction
chemical_list: C514862:Akt1 protein, mouse; C494922:Akt2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B