Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rare syndrome provides clues on obesity, blood pressure

05.03.2008
Research on Bardet-Biedl syndrome helps show how resistance to leptin might disrupt brain signals

University of Iowa researchers have found a clue about how resistance to the hormone leptin might disrupt the brain signals that tell the body when to stop eating. The research, which focused on the rare genetic disorder Bardet-Biedl syndrome (BBS), also found an association between leptin resistance and high blood pressure.

The findings, which were based on mouse models developed at the UI, have implications for treating BBS as well as obesity and high blood pressure in people without BBS. The study appeared online March 3 in the Journal of Clinical Investigation.

"Bardet-Biedl syndrome is rare but its symptoms, including obesity and increased risk of heart disease, are similar to problems faced by many people without the syndrome," said Kamal Rahmouni, Ph.D., the study's principal investigator and assistant professor of internal medicine at the UI Roy J. and Lucille A. Carver College of Medicine. "Leptin normally suppresses appetite and increases caloric use. The more we know about how leptin and gene defects affect people with BBS, the more likely it is that we can improve treatment for them and people with similar symptoms."

The research builds on previous BBS findings, including research led by current study team member Val Sheffield, M.D., Ph.D., the Martin and Ruth Carver Chair in Genetics and professor of pediatrics at the UI and a Howard Hughes Medical Institute investigator.

Fewer than one in 10,000 people have BBS. Sheffield, who has discovered or co-discovered the majority of the 12 known BBS genes, developed BBS mice that have the same features as the human condition. The study used a mouse model without BBS and three mouse models that each lacks a protein (Bbs2, Bbs4 or Bbs6) due to a BBS gene deletion.

The team measured daily food intake and body weight of each mouse. Some mice also received daily leptin injections. Mice without BBS lost weight when injected with leptin. However, the mice with any of the three types of BBS gene defects did not respond to leptin and gained weight.

Rahmouni, who has expertise in metabolism and obesity, said the hormone leptin is an obvious candidate when looking at causes of weight gain.

"Leptin is made in adipose (fat) tissue and is supposed to decrease fat stores. However, if we find high levels of it in the plasma, and people still are obese, we know it's not acting correctly and that there is leptin resistance," he said.

The team also found that even very young mice with BBS, whose body weights were the same as the non-BBS mice, had high levels of leptin in the plasma, indicating leptin resistance. The team then looked at a specific brain region of mice with BBS to understand why this occurred.

"We know that leptin regulates body weight and food intake through the hypothalamus in the brain. In the mice with BBS, we saw that Pomc, one of the three main genes normally regulated by leptin, was not properly regulated," Rahmouni said.

"This finding allowed us to pinpoint a very specific defect that explains why these mice are obese. The brain normally uses the Pomc gene to tell the body to stop eating, but in the animals with BBS, it doesn't work and so the mice won't feel full. We know that people without this gene have the same symptoms as the mice in our study, so the finding is meaningful," he added.

Rahmouni and colleagues will next examine the specific deficit in the neurons in the brain that might cause the problem with the Pomc (pronounced "pom-c") gene.

In another aspect of the study, the team saw that two of the three mouse models with BBS protein problems (Bbs4 and Bbs6) had high blood pressure. Recent research published by another institution has pointed to the same problem in humans with the same gene defects.

The UI team found that using a chemical to block neurotransmission in mice with the Bbs4 and Bbs6 gene defects lowered blood pressure.

"Because there are so few people with BBS, mouse models are very helpful in trying to understand the blood pressure problem," Rahmouni said. "Currently, there is no specific recommendation on what drug or level of drug to use to treat hypertension in BBS patients. In addition, this work may lead to improved treatment of hypertensive patients without BBS. We hope to learn more about the mechanism in order to improve and even customize treatment."

Becky Soglin | EurekAlert!
Further information:
http://www.uiowa.edu

More articles from Health and Medicine:

nachricht Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center

nachricht Study advances gene therapy for glaucoma
17.01.2018 | University of Wisconsin-Madison

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Gran Chaco: Biodiversity at High Risk

17.01.2018 | Ecology, The Environment and Conservation

Only an atom thick: Physicists succeed in measuring mechanical properties of 2D monolayer materials

17.01.2018 | Physics and Astronomy

Fraunhofer HHI receives AIS Technology Innovation Award 2018 for 3D Human Body Reconstruction

17.01.2018 | Awards Funding

VideoLinks
B2B-VideoLinks
More VideoLinks >>>