The role of leptin in regulating bone metabolism

Abstract

Leptin was initially best known for its role in energy homeostasis and regulation of energy expenditure. In the past few years we have realized that leptin also plays a major role in neuroendocrine regulation and bone metabolism. Here, we review the literature the indirect and direct pathways through which leptin acts to influence bone metabolism and discuss bone abnormalities related to leptin deficiency in both animal and human studies. The clinical utility of leptin in leptin deficient individuals and its potential to improve metabolic bone disease are also discussed. We are beginning to understand the critical role leptin plays in bone metabolism; future randomized studies are needed to fully assess the potential and risk-benefit of leptin's use in metabolic bone disease particularly in leptin deficient individuals.

Keywords: Bone; Leptin; Osteoporosis.

Figure 1

Actions of leptin to alter food intake and energy expenditure. Leptin inhibits AGRP/NPY and activates POMC/CART neurons in the arcuate nucleus of the hypothalamus. These neurons in turn act on paraventricular (PVN) neurons to increase or decrease food intake as well as to modulate sympathetic activity and energy expenditure through the Nucleus of the Solitary Tract. Leptin signaling in the hypothalamus also activates other hypothalamic-pituitary-peripheral (HPP) axes, which also have consequences for bone metabolism.