|Title:||Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism|
|Authors:||Brennan-Speranza, Tara C.|
Gasparini, Sylvia J.
Blankenstein, Katharina I.
Cogger, Victoria C.
Cooney, Gregory J.
Dunstanl, Colin R.
Seibel, Markus J.
Discipline of Pharmacology
|Publisher:||American Society for Clinical Investigation|
|Citation:||Brennan-Speranza T.C., Henneicke H., Gasparini S.J., Blankenstein K.I., Heinevetter U., Cogger V.C., Svistounov D., Zhang Y., Cooney G.J., Buttgereit F., Dunstan C.R., Gundberg C., Zhou H., Seibel M.J.. Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism. The Journal of Clinical Investigation. 2012; 122(11):4172-4189. doi:10.1172/JCI63377.|
|Abstract:||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.|
|Department/Unit/Centre:||Discipline of Pharmacology|
|Type of Work:||Article|
|Type of Publication:||Publisher's version|
|Appears in Collections:||Research Papers and Publications. Discipline of Pharmacology|
|Brennan_Speranza_JCI_2012.pdf||4.07 MB||Adobe PDF|