MedWire News: US scientists have found that the hormone leptin, known to suppress appetite, inhibit bone accrual, and reduce energy expenditure, works by inhibiting serotonin levels in the brain stem.
The team from Columbia University Medical Center in New York says their results “identify brain-derived serotonin (BDS) as the long sought-after molecular basis for the common control of bone mass and energy metabolism.”
This could explain why obese patients are less likely than other individuals to develop osteoporosis, comments author Gerard Karsenty who explained that obese individuals have high levels of leptin but do not respond to its signal adequately, leading to an increased appetite and bone mass.
The study, published in the journal Cell, indicates that serotonin inhibits bone mass accrual when present in the duodenum, but increases accrual when produced in the brain stem.
“To our knowledge, this is the first example of a molecule exerting different influences on bone remodelling depending on its site of synthesis,” the researchers note.
Specifically, serotonin’s action in the brain stem is mediated through the 5-hydroxytryptamine receptor 2C in hypothalamic neurons – mice without these receptors are osteopenic even with a healthy metabolism.
Interestingly, the researchers found that although only approximately 5% of bodily serotonin is present in the brain stem, BDS controlled by leptin has a greater impact on bone modelling than serotonin present in the gut.
The researchers suggest that this finding suggests that using leptin to treat for obesity could cause the development of osteoporosis. Conversely, Karentsky said: “It will be difficult to turn on the pathway to strengthen bone without increasing appetite at the same time.”
However, the research showed that serotonin has different receptors for altering bone mass and appetite in the brain stem, added Karentsky.
“Theoretically, one can imagine that a drug that blocks only the appetite receptors, but not the bone receptors, could help people lose weight without losing bone mass.”
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009
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