Hindlimb Immobilization, But Not Castration, Induces Reduction of Undercarboxylated Osteocalcin Associated With Muscle Atrophy in Rats.

Abstract

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.

• Authors: Xuzhu Lin, Erik Hanson, Andrew C Betik, Tara C Brennan-Speranza, Alan Hayes, Itamar Levinger
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 31 Issue 11 Pg. 1967-1978 (11 2016) ISSN: 1523-4681 [Electronic] United States
• PMID: 27291707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 American Society for Bone and Mineral Research.

Chemical References

• Forkhead Transcription Factors
• Hormones
• Insulin Receptor Substrate Proteins
• Irs1 protein, rat
• Osteocalcin
• Mechanistic Target of Rapamycin Complex 1
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Forkhead Transcription Factors (metabolism)
• Hindlimb Suspension
• Hormones (blood)
• Insulin Receptor Substrate Proteins (metabolism)
• Male
• Mechanistic Target of Rapamycin Complex 1 (metabolism)
• Models, Biological
• Muscle, Skeletal (pathology, physiopathology)
• Muscular Atrophy (metabolism, pathology)
• Orchiectomy
• Organ Size
• Osteocalcin (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats, Inbred F344
• Signal Transduction