Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly discovered road map of leptin explains its regulation of bone and appetite

07.09.2009
Leptin-serotonin pathway offers new clues for obesity and osteoporosis prevention

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.

Elizabeth Streich | EurekAlert!
Further information:
http://www.columbia.edu

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Quantum material is promising 'ion conductor' for research, new technologies

17.08.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>