| First Author | Brennan-Speranza TC | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 11 | Pages | 4172-89 |
| PubMed ID | 23093779 | Mgi Jnum | J:194011 |
| Mgi Id | MGI:5470036 | Doi | 10.1172/JCI63377 |
| Citation | Brennan-Speranza TC, et al. (2012) Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism. J Clin Invest 122(11):4172-89 |
| abstractText | Long-term glucocorticoid treatment is associated with numerous adverse outcomes, including weight gain, insulin resistance, and diabetes; however, the pathogenesis of these side effects remains obscure. Glucocorticoids also suppress osteoblast function, including osteocalcin synthesis. Osteocalcin is an osteoblast-specific peptide that is reported to be involved in normal murine fuel metabolism. We now demonstrate that osteoblasts play a pivotal role in the pathogenesis of glucocorticoid-induced dysmetabolism. Osteoblast-targeted disruption of glucocorticoid signaling significantly attenuated the suppression of osteocalcin synthesis and prevented the development of insulin resistance, glucose intolerance, and abnormal weight gain in corticosterone-treated mice. Nearly identical effects were observed in glucocorticoid-treated animals following heterotopic (hepatic) expression of both carboxylated and uncarboxylated osteocalcin through gene therapy, which additionally led to a reduction in hepatic lipid deposition and improved phosphorylation of the insulin receptor. These data suggest that the effects of exogenous high-dose glucocorticoids on insulin target tissues and systemic energy metabolism are mediated, at least in part, through the skeleton. |
