Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Explain How Leptin Regulates Energy Metabolism and Bone Mass

07.09.2009
New research from Columbia University Medical Center has illuminated a previously unknown leptin-serotonin pathway in the brain that simultaneously promotes appetite and bone mass accrual. The research, which explains how leptin – well-known appetite-suppressing hormone – acts in the brain, is published in the Sept. 4 issue of Cell.

When the leptin-serotonin pathway is turned on in mice, the researchers found, appetite increases, the animals eat more, gain weight, and their bone mass increases. When the pathway is turned off, mice eat less, lose weight, and their bones weaken.

Furthermore, leptin was found to not act in the hypothalamus as previously thought, but in the brain stem acting on serotonin, a hormone that in the brain acts to control appetite, mood and anger.

The identification of this pathway helps explain why, as doctors have long known, obese people tend to have a significantly lower prevalence of osteoporosis, says 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. Though obese people produce high levels of leptin, they are resistant, or unresponsive, to its signals – instead, they operate in a false state of leptin deficiency, which increases serotonin – and thereby, appetite and bone mass. Dr. Karsenty points out that these current findings may have more influence on developing a new way to reduce appetite and obesity than preventing osteoporosis.

“It will be difficult to turn on the pathway to strengthen bone without increasing appetite at the same time,” Dr. Karsenty said. “But this finding shows that it is feasible to alter parts of the leptin-serotonin pathway to decrease appetite without weakening bone.”

HORMONE LEPTIN SUPRESSES BONE FORMATION BY SHUTTING OFF SEROTONIN

Dr. Karsenty and his colleagues discovered this pathway after first noticing the powerful effect of leptin – known for suppressing appetite – on bone mass accrual. Dr. Karsenty previously discovered that leptin is the most powerful inhibitor of bone formation in the body. This new study reveals that high levels of leptin suppress bone formation by shutting off the synthesis of serotonin in certain neurons in the brainstem.

Dr. Karsenty and his colleagues were surprised to observe that increased serotonin in the brainstem also increased appetite in mice. “We previously thought that leptin’s modes of action on appetite and bone mass accrual were distinct,” Dr. Karsenty said. “But we found instead that they behave more like twins – taking the same pathway through the brainstem. This correlates strikingly with the fact that leptin appears during evolution of bone cells when bone is first formed in the body.”

Dr. Karsenty’s team found that the appetite and bone pathways diverge once serotonin is released: one set of serotonin receptors turns on appetite, while a second increases bone mass accrual.

The findings may open the door for weight loss drugs that have no side effects on bone density.

“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,” Dr. Karsenty said.

Dr. Karsenty explained the surprising link between appetite and the skeleton by noting that the pathway monitors the amount of energy available to maintain bone.

“Our bones are constantly broken down and rebuilt during our lifetimes, and those renovations require an enormous and daily supply of energy,” he said.

DISCOVERY CLARIFIES PREVIOUS RESEARCH; ADDS TO WORK ON BONE

In November 2008, Dr. Karsenty published a paper in Cell, which describes how serotonin released from the gut controls bone formation. Unlike the brain’s serotonin, an increase in gut serotonin impairs bone formation. (A press release about the Nov. 2008 finding is available at: http://www.cumc.columbia.edu/news/press_releases/Karsenty-cell-serotonin-lrp5.html.)

Dr. Karsenty’s new research shows that while both derivations of serotonin influence bone mass, the brain’s serotonin dominates the effect of serotonin from the gut.

LEPTIN-SEROTONIN PATHWAY MAY ALSO EXPLAIN OSTEOPOROSIS/ANTI-DEPRESSANT LINK

In some studies, selective serotonin reuptake inhibitors (SSRIs), which are commonly used to treat depression, have been associated with osteoporosis in some patients.

SSRIs enhance the action of serotonin, and depending on the person, that may lead to weakened, or strengthened bones, says study co-author J. John Mann, M.D., Ph.D., professor of translational neuroscience (in psychiatry and in radiology) and vice chair for Research in the Department of Psychiatry at Columbia University Medical Center and the New York State Psychiatric Institute.

“SSRIs work in the brain and in the gut, but in some people they may work more strongly in the gut,” Dr. Mann said. “In that case, SSRIs could lead to a decrease in bone growth and osteoporosis.”

The hope is that these research findings will help explain this phenomena and lead to potential treatment for this side effect.

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future health care leaders at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia’s College of Physicians & Surgeons was the first in the country to grant the M.D. degree. Columbia University Medical Center is home to the largest medical research enterprise in New York City and state and one of the largest in the United States.

| Newswise Science News
Further information:
http://www.cumc.columbia.edu

More articles from Life Sciences:

nachricht Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg

nachricht Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Rapid environmental change makes species more vulnerable to extinction

19.10.2017 | Life Sciences

Integrated lab-on-a-chip uses smartphone to quickly detect multiple pathogens

19.10.2017 | Interdisciplinary Research

Fossil coral reefs show sea level rose in bursts during last warming

19.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>