Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Leptin-signaling protein maintains normal body weight and energy balance in mice

17.08.2005


SH2-B enhances brain’s leptin sensitivity

What do laboratory mice at the University of Michigan Medical School have in common with millions of overweight Americans? Like many of us, these mice just can’t stop eating. They weigh twice as much as their littermates, consume nearly two times as much food, have elevated fatty acid and triglyceride levels, are resistant to insulin, and often develop type 2 diabetes.

Scientists at the University of Michigan Medical School are studying these mice to find out what causes their over-eating and morbid obesity. Is it a character flaw? Do the mice lack self-discipline? Is it from living in a fast-food society? How about the absence of a signaling molecule called SH2-B?



Liangyou Rui, Ph.D., an assistant professor of molecular and integrative physiology in the U-M Medical School, says the answer is SH2-B – a protein he discovered eight years ago while he was a U-M graduate student.

"SH2-B is an intracellular signaling molecule that increases the body’s sensitivity to leptin, a hormone which regulates energy balance and body weight in humans and animals," Rui says. "SH2-B interacts with JAK2 – a key signaling protein that mediates how cells respond to a variety of hormones, including leptin."

One of several hormones produced by fat tissue, leptin’s job is to keep the brain informed about the amount and availability of nutrients stored in body fat.

"We believe leptin sensitivity is determined by a balance between positive and negative regulators," Rui explains. "Previously we only knew the negative regulators. Now we’ve demonstrated that SH2-B is the first example of an intracellular signaling protein with a positive, rather than negative, effect on leptin signal transduction. Our research with mice that lack the SH2-B gene, and so can’t make SH2-B protein, indicates its presence is required to maintain normal energy metabolism and body weight in mice."

The latest U-M research results on SH2-B and how it regulates the brain’s sensitivity to leptin will be published in the August 2005 issue of Cell Metabolism.

"The more fat you have in your body, the higher the concentration of leptin in the bloodstream," Rui says. "Leptin sends a powerful signal to the brain saying: We have a surplus. Reduce feeding and increase energy expenditures."

Leptin’s signal is received by the hypothalamus – the part of the brain that regulates the endocrine system and the autonomic nervous system. In response, neurons in the hypothalamus send out chemical signals called neuropeptides, which suppress appetite and make us stop eating. When the system works properly, the body maintains a natural balance between energy taken in as food and energy expended in activity.

"It’s like the feedback mechanism on a thermostat set to maintain room temperature at 72 degrees," Rui explains. "Our brain has a similar set point for body weight, which is different for every person, because it is determined by genetics subject to modification by environmental factors. Sensitivity to leptin in the hypothalamus may be a key determinant of this set point."

When leptin travels through the bloodstream and reaches the hypothalamus, two types of neurons respond to its signal. Orexigenic neurons produce neuropeptides that promote eating. Neuropeptides produced by anorexigenic neurons, on the other hand, inhibit eating. To send its "stop eating" signal, leptin increases production of anorexigenic neuropeptides, while it inhibits production of orexigenic neuropeptides.

When Rui’s research team measured neuropeptides produced by hypothalamic neurons in mice without SH2-B and compared results to those from normal mice, they found major differences.

"Even though blood levels of leptin in SH2-B null mice were dramatically higher than in normal littermate controls, orexigenic neuropeptide levels were twice as high as in normal mice," says Decheng Ren, Ph.D., U-M research fellow and first author of the Cell Metabolism study. "Deleting SH2-B impairs the sensitivity of these hypothalamic neurons to leptin, and may contribute to over-eating and obesity in SH2-B null mice."

To see whether metabolic differences in energy expenditure, rather than over-eating, were responsible for the obesity of the SH2-B null mice, Ren measured oxygen intake, carbon dioxide production and body heat produced during a 24-hour cycle.

"Surprisingly, mice deficient in SH2-B consumed much more oxygen and generated more carbon dioxide and body heat than normal mice," Ren says. "Overall, their energy expenditure was 63 percent higher than littermate controls. But even though their energy expenditures were higher, mice without SH2-B still become obese, primarily because of their extreme over-eating."

Injecting SH2-B deficient mice with supplemental mouse leptin didn’t affect their food intake or weight gain, although it significantly reduced both weight and eating behavior in normal control mice.

"These results demonstrate that deletion of the SH2-B gene causes severe leptin resistance, which appears to be the major factor responsible for obesity in our experimental mice," Rui says.

In future research, Rui hopes to learn exactly how SH2-B modulates leptin sensitivity in deferent hypothalamic neurons, and hopes to learn more about the set point for energy homeostasis and body weight in the brain. He also will continue his previous research on how SH2-B contributes to the development of insulin resistance and type 2 diabetes. And he wants to join forces with a clinical collaborator to screen patients with obesity and diabetes for potential mutations in the human SH2-B gene.

Sally Pobojewski | EurekAlert!
Further information:
http://www.umich.edu

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>