Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New insight into how serotonin reduces appetite could help in developing safer anti-obesity drugs

20.07.2006
A study led by a UT Southwestern Medical Center researcher sheds light on how the brain chemical serotonin, when spurred by diet drugs such as Fen-phen, works to curb appetite.

That knowledge could aid in the design of safer anti-obesity drugs nearly a decade after Fen-phen was banned for causing harmful side effects.

The study, which tested the effect of several drugs that alter serotonin levels in the brain, found that serotonin activates some neurons and melanocortin-4 receptors, or MC4Rs, to curb appetite and at the same time blocks other neurons that normally act to increase appetite.

The dual effect helps explain how such drugs, including Fen-phen, spur weight loss.

The finding, available online and in the July 20 issue of Neuron, also reinforces the role of serotonin – a regulator of emotions, mood and sleep – in affecting the brain's melanocortin system, a key molecular pathway that controls body weight.

"The more we understand about the pathways and the way serotonergic drugs regulate body weight, the more it one day might lead to harnessing beneficial properties of anti-obesity treatments like Fen-phen and minimizing the harmful side effects," said Dr. Joel Elmquist, professor of internal medicine at UT Southwestern and co-senior author of the study.

In the United States, about 66 percent of adults are obese or overweight, as are 16 percent of young people aged 6 to 19, according to the Centers for Disease Control and Prevention. The trend is significant because being overweight or obese increases the risk of harmful health consequences, such as heart disease, stroke, diabetes, non-alcoholic liver disease and death.

Drugs that enhance the brain's release of serotonin have helped people lose weight. Fen-phen, which paired fenfluramine with phentermine, had such success. The drug combination, however, also led some patients to develop cardiac complications, Dr. Elmquist said. The drug was removed from the market in 1997.

But the mechanisms of how it caused weight loss were never fully determined, he said.

So a few years ago, Dr. Elmquist and his research team set out to detail how fenfluramine affected the brain's molecular pathways to reduce appetite. In 2002, they examined the region of the brain's hypothalamus containing the arcuate nucleus, or ARC. In the ARC, drug-induced serotonin activates brain cells called pro-opiomelanocortin neurons, or POMC, which in turn release a hormone that acts on the MC4R to reduce appetite.

The team's new study shows how serotonin also simultaneously blocks other neurons, known as NPY/AgRP, from being able to inhibit activity of MC4Rs. By blocking this inhibitory activity, serotonin prevents an increase in appetite.

Researchers studied the effect of Fen-phen and other serotonin-inciting drugs on both normal and genetically engineered lean and obese mice. They found that serotonin's dual regulation of POMC and AgRP neurons is necessary to promote weight loss.

"The finding increases the understanding of the molecular circuitry that controls body weight in response to changing levels of serotonin," Dr. Elmquist said. "An overarching goal of this understanding, for humans, is to design specific, safe drugs to fight obesity."

Dr. Elmquist, who recently left Harvard Medical School, directs the newly formed Center for Hypothalamic Research at UT Southwestern. The center, along with the Taskforce for Obesity Research, a National Institutes of Health Interdisciplinary Research Center, is part of the institution's effort to investigate the causes of obesity, metabolic syndrome and diabetes.

Cliff Despres | EurekAlert!
Further information:
http://www.utsouthwestern.edu

More articles from Life Sciences:

nachricht What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

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

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>