Leptin regulation of the sympathetic nervous system control of bone mass. Leptin, secreted from adipose tissue, crosses the blood brain barrier and acts through the leptin receptor (ObR) to inhibit serotonin (5-HT) production in serotonin-containing neurons in the brainstem. Normally, serotonin would be secreted from these nerve terminals in the ventromedial hypothalamus (VMH) to suppress sympathetic activity to bone. However, under leptin-induced inhibition of serotonin synthesis, the sympathetic nervous system (SNS) signals to osteoblasts by releasing norepinephrine (NE) onto β2-adrenergic receptors (Adrb2). This in turn suppresses bone formation and increases resorption through increased RANKL expression.