BoneKEy Reports | BoneKEy Watch
The effect of glucocorticoids on energy metabolism is mediated by osteoblasts
DOI:10.1038/bonekey.2012.254
Glucocorticoid-induced metabolic disorders may have a skeletal component; in this study, two experimental methods in mice were devised to uncover the role of mature osteoblasts.
The first used a transgenic mouse model in which transgenic (Tg) mice had osteoblasts with severely impaired glucocorticoid signaling. Tg mice accumulated fat and developed hyperlipidemia when treated with corticosterone, suggesting that fuel metabolism is affected by the action of glucocorticoids on osteoblasts. Insulin resistance tests revealed that wild-type (WT) mice developed insulin resistance early, usually by day 7 of corticosterone treatment, while Tg mice remained insulin sensitive. Most showed only partial insulin resistance from day 14. Although Tg mice did not show the changes in fasting glucose observed in WT mice, they did demonstrate the significant increase in serum insulin normally associated with corticosterone therapy.
In the second approach, WT mice were given gene therapy to induce endogenous heterotopic (hepatic) expression of uncarboxylated and carboxylated osteocalcin. When treated with corticosterone, these mice showed a similar response to Tg mice – greater insulin sensitivity, less glucose intolerance and less weight gain.
Editor’s comment: Although osteocalcin is increasingly recognized as a regulator of glucose metabolism, its role in pathophysiological processes remains unclear. This elegant study demonstrates that the metabolic complications of glucocorticoid administration are at least partly mediated by glucocorticoid receptor signaling in osteoblasts and by the suppression of osteocalcin expression. Could treating Glucocorticoid-Induced Osteoporosis Program patients with parathyroid hormone, a potent inducer of osteocalcin expression, therefore improve their impaired glucose metabolism? In addition, some of the observations made in this paper are substantially different from those of previous studies and need to be explored further.
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