New Understanding of Leptin’s Role in Appetite and Bone Mass Could Lead to Treatment for Obesity

Scientists have noted for a long time that the hormone leptin suppresses appetite. That’s why they have been puzzled by the high levels of leptin found in obese people-shouldn’t leptin decrease their appetites and act as a curb on their weight? Leptin also suppresses bone mass accrual, yet obese people do not suffer from loss or weakening of bone mass, despite their high leptin levels.

Why leptin acts in these seemingly contradictory ways in obese people has been a mystery until now, but in a recently published study, researchers say they believe that they have solved it. The study’s senior author, Gerard Karsenty, M.D., Ph.D., chair of the Department of Genetics & Development at Columbia University’s College of Physician and Surgeons, and his colleagues have found that leptin controls the amount of serotonin in the brain, a hormone that affects appetite and mood. An abundance of serotonin leads to greater appetite and increased bone mass-something high levels of leptin should prevent.

They also found that although obese people produce high levels of leptin, their bodies are unresponsive, or even resistant, to it (a condition much like insulin resistance among people with type 2 diabetes). As a result, they live in a state of leptin pseudo- deficiency. With leptin failing to function as a control, their bodies produce more serotonin and, thus, greater appetite and bone mass.

Insights from this research could lead to ways of using the leptin-serotonin pathway to control appetite, thereby helping obese people lose weight. The problem that the Columbia scientists face, though, is how to separate leptin’s closely bound effects on appetite and bone mass from each other. Will it be possible to use leptin to suppress serotonin’s appetite-enhancing effects without interfering with serotonin’s positive role in bone formation?

The research, which was published in the September 4 issue of Cell, builds on a previous discovery that leptin, besides its appetite-suppressing powers, is the body’s most powerful suppressor of bone formation. The Columbia team discovered that it does so by shutting off the production of serotonin in the brainstem, a process not previously suspected.

The insights about leptin and serotonin also provide an unexpected link between appetite and bone formation. The link makes sense considering the immense amount of energy needed to maintain or rebuild bone-energy derived from food delivered by an active appetite. 

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Research article in Cell

e! Science News article

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