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Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism

Tara C Brennan-Speranza1, Holger Henneicke, Sylvia J Gasparini

  • 1Bone Research Program, ANZAC Research Institute, University of Sydney, Sydney, Australia. tara@anzac.edu.au

The Journal of Clinical Investigation
|October 25, 2012
PubMed

Insights

Glucocorticoids disrupt metabolism by affecting the skeleton. Targeting osteoblasts or boosting osteocalcin levels can prevent these adverse effects, revealing a key role for bone in glucocorticoid-induced metabolic dysfunction.

Area of Science:

  • Endocrinology
  • Metabolic Science
  • Bone Biology

Background:

  • Long-term glucocorticoid use causes adverse metabolic effects like weight gain, insulin resistance, and diabetes.
  • The mechanisms behind these side effects are not fully understood.
  • Glucocorticoids inhibit osteoblast function and osteocalcin synthesis, a peptide involved in fuel metabolism.

Purpose of the Study:

  • To investigate the role of osteoblasts and osteocalcin in the pathogenesis of glucocorticoid-induced metabolic dysfunction.
  • To determine if skeletal manipulation can prevent or mitigate these adverse effects.

Main Methods:

  • Osteoblast-specific disruption of glucocorticoid signaling in mice treated with corticosterone.
  • Gene therapy to restore carboxylated and uncarboxylated osteocalcin levels in glucocorticoid-treated mice.
  • Assessment of insulin resistance, glucose tolerance, weight gain, and hepatic lipid deposition.

Main Results:

  • Disrupting glucocorticoid signaling in osteoblasts prevented insulin resistance, glucose intolerance, and weight gain in treated mice.
  • Restoring osteocalcin levels via gene therapy mimicked these protective effects and reduced liver fat.
  • Improved insulin receptor phosphorylation was observed with osteocalcin restoration.

Conclusions:

  • Osteoblasts play a critical role in the development of glucocorticoid-induced metabolic disturbances.
  • The skeleton, through osteocalcin, is a key mediator of glucocorticoid effects on systemic energy metabolism and insulin sensitivity.

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