Navigation Links
Weight control protein may yield antiobesity drugs

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?9 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.


'"/>

Source:Cell Press


Related biology news :

1. Leptin-signaling Protein Maintains Normal Body Weight And Energy Balance In Mice
2. Weighting cancer drugs to make them hit tumors harder
3. Weighty viruses
4. Ancient olfaction protein is shared by many bugs, offering new pest control target
5. Gene variations explain drug dose required to control seizures
6. U-M scientists find genes that control growth of common skin cancer
7. Scientists discuss improved biopesticides for locust control in West Africa
8. Insight into natural cholesterol control suggests novel cholesterol-lowering therapy
9. To control germs, scientists deploy tiny agents provocateurs
10. Cooperation is key—a new way of looking at MicroRNA and how it controls gene expression
11. Master gene controls healing of skin in fruit flies and mammals
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/30/2017)... ARLINGTON, Va. , June 30, 2017 /PRNewswire-USNewswire/ ... a leading developer and supplier of face and ... the ATA Featured Product provider program. ... created an innovative way to monitor a driver,s ... benefit greatly from being able to detect fatigue ...
(Date:5/23/2017)... May 23, 2017  Hunova, the first robotic gym for the rehabilitation ... officially launched in Genoa, Italy . The first 30 ... and the USA . The technology was developed and ... by the IIT spin-off Movendo Technology thanks to a 10 million euro ... Release, please click: ...
(Date:5/6/2017)... 5, 2017 RAM Group , ... new breakthrough in biometric authentication based on a ... properties to perform biometric authentication. These new sensors are ... created by Ram Group and its partners. This sensor ... supply chains and security. Ram Group is a ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... The ... three Winners and six Finalists of the 2017 Blavatnik Regional Awards for Young ... Family Foundation and administered by the New York Academy of Sciences to honor ...
(Date:10/12/2017)... ... October 12, 2017 , ... ... first-ever genomics analysis platform specifically designed for life science researchers to analyze ... pioneering researcher Rosalind Franklin, who made a major contribution to the discovery ...
(Date:10/11/2017)... ... October 11, 2017 , ... Proscia Inc ... hosting a Webinar titled, “Pathology is going digital. Is your lab ready?” with ... adoption best practices and how Proscia improves lab economics and realizes an increase ...
(Date:10/11/2017)... (PRWEB) , ... October 11, 2017 , ... ... Administration (FDA) has granted orphan drug designation to SBT-100, its novel anti-STAT3 (Signal ... the treatment of osteosarcoma. SBT-100 is able to cross the cell membrane and ...
Breaking Biology Technology: