Leptin: cutting the fat off the bone

• Published in: The Lancet (British edition) 2003-11, Vol.362 (9395), p.1572-1574
• Main Authors: Cock, Terrie-Anne, Auwerx, Johan
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - pharmacology; Animals; Anorexia; Biochemistry, Molecular Biology; Biological and medical sciences; Biomedical materials; Blood pressure; Bone Density - drug effects; Bone Density - physiology; Bones; Brain stem; Cardiovascular diseases; Cocaine; Congenital diseases; Deletion; Density; Disease control; Energy; Energy balance; Energy Metabolism - drug effects; Energy Metabolism - physiology; Food; Genetics; Gold; Hormones; Humans; Hypothalamus - drug effects; Hypothalamus - physiology; In vivo methods and tests; Investigative techniques, diagnostic techniques (general aspects); Leptin; Leptin - pharmacology; Leptin - physiology; Life Sciences; Maintenance; Medical sciences; Metabolic diseases; Mice; Mice, Obese; Nervous system; Neural Pathways - drug effects; Neural Pathways - physiology; Neurons - drug effects; Neurons - physiology; Neuropeptides; Norepinephrine; Nutritional status; Obesity; Osteoblasts; Osteogenesis - drug effects; Osteogenesis - physiology; Osteoporosis; Osteoporosis - drug therapy; Outflow; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Physiology; Propranolol - pharmacology; Receptors; Receptors (physiology); Rodents; Sympathetic nervous system; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiology
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(03)14747-2

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. 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.