Glucocorticoids, bone and energy metabolism

Area of Science:

• Endocrinology
• Metabolic Diseases
• Bone Biology

Background:

• Glucocorticoids (GCs) cause adverse metabolic effects like insulin resistance and altered body composition.
• Traditionally, these effects were attributed to direct GC action on liver and adipose tissue.
• Emerging evidence suggests bone cells, specifically osteoblasts, mediate some GC-induced metabolic changes.

Purpose of the Study:

• To investigate the role of osteoblasts and osteocalcin in mediating GC-induced metabolic alterations.
• To explore the connection between bone and systemic fuel metabolism under GC excess.
• To highlight the need for human studies on GC-bone-metabolism interactions.

Main Methods:

• Studies in mice involving targeted disruption of GC signaling in osteoblasts.
• Analysis of body composition and systemic fuel metabolism during GC treatment.
• Investigating the metabolic effects of heterotopic osteocalcin expression in the liver.

Main Results:

• Abrogating GC signaling in mouse osteoblasts significantly reduced GC-induced changes in body composition and metabolism.
• Osteocalcin expression in the liver protected against GC-induced metabolic disturbances.
• These findings implicate osteocalcin as a key mediator linking bone and systemic fuel metabolism.

Conclusions:

• Glucocorticoid-induced metabolic dysfunction is, in part, mediated by actions on bone osteoblasts.
• Osteocalcin plays a crucial role in connecting bone health to systemic fuel metabolism.
• Further human research is essential to confirm the extent to which bone mediates GC-induced metabolic changes.