Leptin and Bone

Bone grows then constantly renews itself during adulthood through the succession of cycles of formation by osteoblasts and resorption by osteoclasts. This is a costly process in terms of energy that needs to be coordinated with the amount of available resources, suggesting that bone and appetite and/or energy metabolisms could share common regulator(s). Searching for such molecule(s) identified leptin as a major inhibitor of bone mass accrual that uses central relays to fulfill this function. One of them involves a brain serotonin-dependent regulation of the sympathetic tone, which acts as an inhibitor of bone formation via CREB and the molecular clock and as a positive regulator of bone resorption through an ATF4-Rankl mechanism that takes place in osteoblasts. In contrast, the second mediator of leptin central effect on bone mass accrual, CART, inhibits bone resorption. This chapter details the molecular bases and biological relevance of this regulation of bone mass accrual by leptin.