Hindlimb Immobilization, But Not Castration, Induces Reduction of Undercarboxylated Osteocalcin Associated With Muscle Atrophy in Rats.
Undercarboxylated osteocalcin (ucOC) has been implicated in skeletal muscle insulin sensitivity and function. However, whether muscle mass and strength loss in atrophic conditions is related to a reduction in ucOC is not clear. We hypothesized that both immobilization and testosterone depletion would lead to reductions in ucOC, associated with not only the degree of muscle atrophy but also changes to atrophy signaling pathway(s) in male rats. We subjected 8-week-old male Fischer (F344) rats to 7 days of hindlimb immobilization 10 days after castration surgery. Hindlimb immobilization, but not castration, resulted in a significant reduction in ucOC (30%) and lower ucOC was correlated with the degree of muscle loss and muscle weakness. ucOC levels, the expression of ucOC-sensitive receptor G protein-coupled receptor, class C, group 6, member A (GPRC6A), as well as the activity of extracellular signal-regulated kinase (ERK) and 5' adenosine monophosphate-activated protein kinase (AMPK) were associated with the expression and activity of a number of proteins in the mammalian target of rapamycin complex 1 (mTORC1) and Forkhead Box O (FOXO) signaling pathways in a muscle type-specific manner. These data suggest that ucOC may have other effects on skeletal muscle in addition to its insulin sensitizing effect. © 2016 American Society for Bone and Mineral Research.
Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia.
Xuzhu
X
Lin
Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia.|College of Health and Biomedicine, Victoria University, Melbourne, Australia.
Erik
E
Hanson
Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia.|College of Health and Biomedicine, Victoria University, Melbourne, Australia.
Andrew C
AC
Betik
Department of Physiology and Bosch Institute for Medical Research, University of Sydney, Australia.
Tara C
TC
Brennan-Speranza
Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia.|College of Health and Biomedicine, Victoria University, Melbourne, Australia.|Australian Institute for Musculoskeletal Science, Western Health, Melbourne, Australia.
Alan
A
Hayes
Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia.
Itamar
I
Levinger
D000818:Animals; D051858:Forkhead Transcription Factors / Q000378:metabolism; D019417:Hindlimb Suspension; D006728:Hormones / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology*; D009919:Orchiectomy; D009929:Organ Size; D015675:Osteocalcin / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011916:Rats, Inbred F344; D015398:Signal Transduction
D051858:Forkhead Transcription Factors; D006728:Hormones; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D015675:Osteocalcin; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt
CASTRATION; HINDLIMB IMMOBILIZATION; MUSCLE ATROPHY; TESTOSTERONE; UNDERCARBOXYLATED OSTEOCALCIN