Leptin: cutting the fat off the bone.

Context: Leptin was initially proposed to be the antiobesity hormone. Now it is realised that leptin is more a signal molecule that communicates nutritional status to the brain, and that it is involved in bone formation by having an antiosteogenic action.

Starting Point: Recently, Florent Elefteriou and colleagues (Endocrinology 2003; 144: 3842-47) found that hypothalamic neurons control bone mass. These researchers used monosodium glutamate to obliterate neurons in the arcuate nucleus. Previously, this group (Cell 2002; 101: 305-17) had shown that leptin inhibits bone formation by modulating the sympathetic nervous system. Although leptin influences both energy balance and bone mass by acting on the hypothalamus, the two processes involve different proteins and neurons. WHERE NEXT? Leptin has antiosteogenic activity in mice, mediated by hypothalamic nervous pathways and the sympathetic nervous system. Yet some human studies dispute leptin's antiosteogenic role. Large clinical studies are necessary to consolidate leptin's role in the physiology of human bone. In mice the beta blocker propranolol, a widely used drug with no major deleterious effects, significantly increases bone formation and bone mass without affecting bodyweight, a finding that may provide novel opportunities to design efficient bone-forming drugs for human beings.