Osteocalcin: an osteoblast-derived polypeptide hormone that modulates whole body energy metabolism

Osteocalcin is a bone-specific protein that is regularly used in the clinical setting as a serum marker of bone turnover. Recent evidence indicates that osteocalcin plays a previously unsuspected role in the control of energy metabolism. Thus, osteocalcin-deficient mice have a profoundly deranged metabolic phenotype that includes insulin resistance, glucose intolerance and abnormal fat deposition. Additionally, osteocalcin administration in mice improves insulin sensitivity and decreases fat pad mass and serum triglyceride levels. The role of osteocalcin in human macronutrient metabolism is less clear but recent studies report positive correlations between serum osteocalcin levels and established indices of metabolic health. Herein, we review key physiological functions of osteocalcin, focussing on the roles of osteocalcin in the modulation of macronutrient metabolism, male reproductive function and foetal brain development. We consider the implications of these findings for the coordination of metabolism with development and fertility. We also consider evidence that a Class C G-protein-coupled receptor from a subgroup known to mediate nutrient-sensing acts as the osteocalcin receptor.