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 Closing the carbon loop
08.12.2016 | University of Pittsburgh

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>