Leptin and bone

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The fact that leptin, a hormone released from fat tissue, can regulate bone mass first came to prominence in 2000 [1]. It is now well established that leptin can affect bone metabolism via direct signalling from the brain and that although leptin acts to reduce cancellous bone, it conversely increases cortical bone. A number of theories have been put forward concerning the cortical-cancellous dichotomy including a recent theory suggesting that increased leptin during obesity may represent a mechanism for enlarging bone size and thus bone resistance to cope with increased body weight [2].

Bone metabolism is under direct control of the brain and thus nerve fibres are present in bone tissue [3]. A number of brain signalling molecules (neuropeptides and neurotransmitters) have been found in bone including adrenaline, noradrenaline, serotonin, calcitonin gene-related peptide, vasoactive intestinal peptide and neuropeptide Y [4] [5]. This evidence supports a direct signalling system between the brain and bone with accumulating evidence suggesting that these molecules are directly involved in the regulation of bone metabolism. Leptin, once released from fat tissue, can cross the blood-brain barrier and bind to its receptors in the brain where it acts through the sympathetic nervous system to regulate bone metabolism [6].

It is also possible that, in addition to its effects through the brain, leptin may act directly on cells in the bone to regulate bone metabolism. In reality, leptin probably signals to bone on multiple levels, with local and systemic checks and balances impacting the final outcome. As a result, the clinical utility of leptin for treatment of bone diseases remains open but ongoing research may yet provide much needed therapies for stimulating bone formation.

[edit] References

  1. ^ Ducy P, Amling M, Takeda S, et al.: Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 2000, 100:197-207
  2. ^ Hamrick MW, Ferrari SL.: Leptin and the sympathetic connection of fat to bone. Osteoporos Int 2007
  3. ^ Allison SJ, Herzog H.: NPY and bone. Exs 2006, 171-82
  4. ^ Allison SJ, Herzog H.: NPY and bone. Exs 2006, 171-82
  5. ^ Gordeladze JO, Reseland JE.: A unified model for the action of leptin on bone turnover. J Cell Biochem 2003, 88:706-12
  6. ^ Takeda S, Elefteriou F, Levasseur R, et al.: Leptin regulates bone formation via the sympathetic nervous system. Cell 2002, 111:305-17