Featured Research

from universities, journals, and other organizations

Roadmap Of Leptin Explains Its Regulation Of Bone And Appetite: New Clues For Obesity And Osteoporosis Prevention

Date:
September 11, 2009
Source:
Columbia University Medical Center
Summary:
New research has illuminated a previously unknown leptin-serotonin pathway in the brain that simultaneously promotes appetite and bone mass accrual. The research explains how leptin -- well-known appetite-suppressing hormone -- acts in the brain.

This figure (Figure 7 from Cell paper) is a schematic representation of the pathway used by leptin in the brain to inhibit both bone mass accrual and appetite. It has been assumed that leptin acts in the hypothalamus to regulate these two functions, but inactivation of the leptin receptor in hypothalamic neurons affects neither bone mass nor appetite. This suggests that in fact leptin does not act in the hypothalamus. In this issue of Cell, Yadav et al. show that leptin regulates these two physiological functions by inhibiting serotonin synthesis and release in brainstem, which acts in the hypothalamus through three serotonin receptors (Htr1a, 2b and 2C) present on specific nuclei. These results modify the map of leptin signaling in the brain and indicate that the serotonergic neurons exert a more fundamental influence on several homeostatic functions than previously thought.
Credit: Columbia University Medical Center

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.

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.


Story Source:

The above story is based on materials provided by Columbia University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Vijay K. Yadav, Franck Oury, Nina Suda, Zhong-Wu Liu, Xiao-Bing Gao, Cyrille Confavreux, Kristen C. Klemenhagen, Kenji F. Tanaka, Jay A. Gingrich, X. Edward Guo, Laurence H. Tecott, J. John Mann, Rene Hen, Tamas L. Horvath, Gerard Karsenty. A Serotonin-Dependent Mechanism Explains the Leptin Regulation of Bone Mass, Appetite, and Energy Expenditure. Cell, 2009; DOI: 10.1016/j.cell.2009.06.051

Cite This Page:

Columbia University Medical Center. "Roadmap Of Leptin Explains Its Regulation Of Bone And Appetite: New Clues For Obesity And Osteoporosis Prevention." ScienceDaily. ScienceDaily, 11 September 2009. <www.sciencedaily.com/releases/2009/09/090903163552.htm>.
Columbia University Medical Center. (2009, September 11). Roadmap Of Leptin Explains Its Regulation Of Bone And Appetite: New Clues For Obesity And Osteoporosis Prevention. ScienceDaily. Retrieved July 26, 2014 from www.sciencedaily.com/releases/2009/09/090903163552.htm
Columbia University Medical Center. "Roadmap Of Leptin Explains Its Regulation Of Bone And Appetite: New Clues For Obesity And Osteoporosis Prevention." ScienceDaily. www.sciencedaily.com/releases/2009/09/090903163552.htm (accessed July 26, 2014).

Share This




More Health & Medicine News

Saturday, July 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins