Skeletal research is currently undergoing a period of marked expansion. One aspect in particular is the relationship between bone and fat metabolism. Emerging evidence indicates that bone and adipose activity are co-regulated and inter-dependent.
Signals from fat cells are known to regulate bone mass, with prominent adipokines such as leptin and adiponectin. One bone/fat-active pathway is controlled by neuropeptide Y (NPY), most prominently in the hypothalamus, but also in the osteoblast. NPY is a critical downstream mediator of leptin actions, and is fundamental to the skeletal response resulting from hypothalamic leptin signaling. Elevation in central NPY expression produces powerful stimulation of appetite and adipose tissue production, but also inhibition of osteoblast activity, through neural relays from the brain to the bone.
Interestingly, signals produced by bone cells are now being identified that are capable of regulating fat cells, both directly and through central hypothalamic signaling. Osteocalcin, a protein secreted by osteoblasts, is capable of regulating of energy and glucose homeostasis, reducing fat mass and increase insulin sensitivity. We have recently, identified a novel central loop for osteocalcin signalling to regulate bone, but also capable of regulating adipose and glucose homeostasis.
In conclusion, the link between energy and bone homeostasis is far more complex than previously appreciated, with multiple axes of control, involving both central and direct signalling pathways. These signalling axes reveal a classic, hypothalamic pattern of feedback, and efferent neural/endocrine control.