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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>