Leptin and Bone: Does the Brain Control Bone Biology?

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Abstract
The means by which obesity leads to high bone density and protects individuals from osteoporosis is not known. The study of bone biology in two mouse models of obesity, leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice, points to a role for leptin in the control of bone density. When leptin action is missing in these mice, bone density is high. This is true despite concurrent hypogonadism and hypercortisolism, two strong proresorptive signals that would normally lead to low bone density. Curiously, leptin does not have a direct effect on osteoblasts, which suggests the existence of a central, neuroendocrine pathway that controls bone mass.