Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme Action Could Be Target for Diabetes, Heart Disease Treatments

17.11.2010
Cardiac researchers at UC have found a new cellular pathway that could help in developing therapeutic treatments for obesity-related disorders, like diabetes and heart disease.

This research is being presented at the American Heart Association’s Scientific Sessions in Chicago Nov. 16.

Tapan Chatterjee, PhD, and researchers in the division of cardiovascular diseases found that action by the enzyme histone deacetylase 9 (HDAC9) can lead to obesity-induced body fat dysfunction and that HDAC9-regulated pathways could be targets for potential treatment options in obesity-related diseases.

"Failure of fat cells to differentiate and properly store excess calories in obesity is associated with adipose tissue (fat) inflammation, fatty liver disease, insulin resistance, diabetes and increased cardiovascular diseases,” Chatterjee says. "We know that dysfunctional fat tissue is the underlying culprit in obesity-related diseases; however, we do not know why fat tissue becomes dysfunctional when a person becomes obese.”

Chatterjee says researchers in this study first identified HDAC9 regulator of fat cell differentiation within the living organism.

"Caloric intake promotes HDAC9 down-regulation to allow the conversion of precursor fat cells to ‘functional’ fat cells, capable of efficiently storing excess calories for future use and also maintaining whole body lipid and glucose stability,” he says. "Ideally, fat cells should function as a reversible storage site of excess calories and as an endocrine organ to maintain systemic lipid and glucose stability.

"Unfortunately, during chronic over-feeding, we find HDAC9 level is up-regulated in fat tissue, thereby blocking the conversion which leads to adipose tissue dysfunction and the onset of diseases such as diabetes, liver disease, high blood pressure and heart disease—the nation’s No. 1 killer.”

Researchers examined various members of the HDAC family of proteins and found that only HDAC9 showed a direct correlation to differentiation of precursor fat cells, both from human and mouse fat tissues.

"HDAC9 down-regulation is necessary for the differentiation of precursor fat cells to mature fat cells; forced up-regulation of HDAC9 by genetic manipulation blocks the differentiation of the precursor fat cells,” Chatterjee says. "On the other hand, precursor fat cells from HDAC9 genetic knockout mice showed accelerated differentiation.

"We believe that HDAC9 keeps precursor fat cells in the undifferentiated state; metabolic cues trigger HDAC9 down-regulation allowing conversion of the precursor cells to mature fat cells. We are exploring the cellular signaling mechanism that promotes such down-regulation of this enzyme during the normal fat cell differentiation process.”

Chatterjee says researchers were really interested in the tie between increased HDAC9 levels in fat tissue of mice and the caloric overload.

"Fat tissues from these obese mice showed dysfunction, with increased expression of pro-inflammatory agents and decreased expression of hormones responsible for maintaining whole body lipid and glucose stability,” he says. "The fat tissues of these mice are not capable of efficiently storing excess calories and are not able to perform proper endocrine functions.

"The adaptive response fails for some reason during chronic caloric overload, leading to the generation of fat tissue mass that is dysfunctional.”

Chatterjee says the HDAC9 level in fat cells is the underlying molecular culprit for dysfunctional fat tissue during obesity.

"We are currently examining HDAC9 knockout mice subjected to chronic high-fat feeding and think that HDAC9 gene removal will protect mice from obesity-linked adipose tissue dysfunction and associated metabolic disorders,” he says.

"Identification of HDAC9 as a novel regulator of fat cell differentiation and the finding that elevated HDAC9 levels are associated with adipose tissue dysfunction in obesity are extremely interesting and novel findings,” he continues.

Chatterjee’s team is pursuing studies to understand how diet regulates HDAC9 levels in fat tissue and how HDAC9 up-regulation can be prevented during diet-induced obesity through pharmacological means.

"Our findings may help lead researchers to targeted therapies that may prevent the development of obesity-related disorders in humans.”

This study was funded by a grant from the National Institutes of Health.

Katie Pence | EurekAlert!
Further information:
http://www.uc.edu

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

Ultrathin device harvests electricity from human motion

24.07.2017 | Power and Electrical Engineering

Scientists announce the quest for high-index materials

24.07.2017 | Materials Sciences

ADIR Project: Lasers Recover Valuable Materials

24.07.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>