Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Weight control protein may yield antiobesity drugs

17.08.2005


A weight control protein with a key role in the brain’s ability to monitor body fat content may yield new approaches for treating obesity and type 2 diabetes, according to a new report in the August issue of Cell Metabolism. The findings in mice further suggest that particular variants of the protein SH2-B might underlie obesity in humans, the researchers said.



SH2-B, which has multiple functions in cells throughout the body, keeps the brain sensitive to the fat hormone leptin, found researchers from the University of Michigan Medical School. Produced by fat tissue, the leptin hormone sends signals to the brain about the body’s fat content. That signal, in turn, elicits adjustments in appetite and energy expenditure to maintain normal body weight.

Mice lacking SH2-B overeat and become obese, the team found. The animals additionally develop a metabolic syndrome characterized by high blood concentrations of leptin, insulin, and lipids. They also develop fatty livers and high blood sugar, the group reports.


"Our findings reveal SH2-B as an important positive regulator of leptin sensitivity inside cells of the brain region known as the hypothalamus," said senior author of the study, Liangyou Rui. The hypothalamus is a key area in the central nervous system that integrates neuronal, hormonal, and nutrient-related signals to maintain body weight, he explained.

Leptin is a hormone produced by fat that normally decreases food intake and increases energy expenditure. In many species, including humans, the hormone acts to stabilize weight and glucose balance through activating its receptors in the hypothalamus.

Earlier work by Rui’s group found that SH2-B binds to a second protein, JAK2, to promote leptin signaling in cultured cells. Further work then identified a physiological role for SH2-B in the regulation of blood glucose; mice deficient for the protein develop insulin resistance and type 2 diabetes, they found.

The current study shows that SH2-B also regulates energy balance and body weight by enhancing leptin sensitivity in animals, Rui said.

Mice lacking a functional copy of the SH2-B gene were smaller at birth than normal mice. After 5 weeks of age, however, the mice began gaining weight rapidly and were about twice as heavy as normal littermates after several months, with at least a 2.8-fold increase in body fat content.

The mice also exhibited a near doubling of blood lipid levels and their livers grew to more than twice their normal size owing to a massive accumulation of fat, Rui said.

Moreover, the animals developed severely elevated blood sugar, insulin, and leptin concentrations. Elevated leptin levels are a hallmark of leptin resistance, a primary risk factor for obesity, he added.

Further examination found that the animals lacking SH2-B ate nearly twice as much as normal. Surprisingly, Rui said, the animals burned more calories; however, the animals still have a net positive energy imbalance of more than 60% higher than normal animals at 18–19 weeks of age, owing to voracious feeding. The mice also exhibited defects in the leptin signaling pathway in brain cells of the hypothalamus, they report.

Earlier studies have found that mice lacking leptin show marked obesity that is restored following leptin treatment, Rui said. However, obese animals, with high blood concentrations of the hormone, often exhibit resistance to leptin’s usual effects. As a result, leptin itself has proven to be insufficient for obesity therapy.

The new findings reveal SH2-B as a critical component in maintaining leptin sensitivity, Rui said. Therefore, SH2-B and signaling events regulated by SH2-B may serve as potential therapeutic targets for the treatment of obesity and type 2 diabetes.

"Because SH2-B sensitizes both leptin and insulin, action drugs that mimic or enhance SH2-B action may improve insulin and leptin sensitivity and have potential value in treatment of obesity and type 2 diabetes," he added.

Heidi Hardman | EurekAlert!
Further information:
http://www.cellmetabolism.org

More articles from Life Sciences:

nachricht New way to look at cell membranes could change the way we study disease
19.11.2018 | University of Oxford

nachricht Controlling organ growth with light
19.11.2018 | European Molecular Biology Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

New materials: Growing polymer pelts

19.11.2018 | Materials Sciences

Earthquake researchers finalists for supercomputing prize

19.11.2018 | Information Technology

Controlling organ growth with light

19.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>