(Press-News.org) CINCINNATI—Cardiac researchers at the University of Cincinnati (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 Session 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."
INFORMATION:
This study was funded by a grant from the National Institutes of Health.
Enzyme action could be target for diabetes, heart disease treatments
2010-11-17
ELSE PRESS RELEASES FROM THIS DATE:
Detroit's urban farms could provide a majority of produce for local residents
2010-11-17
EAST LANSING, Mich. — Transforming vacant urban lots into farms and community gardens could provide Detroit residents with a majority of their fruits and vegetables.
As city officials ponder proposals for urban farms, a Michigan State University study indicates that a combination of urban farms, community gardens, storage facilities and hoop houses – greenhouses used to extend the growing season – could supply local residents with more than 75 percent of their vegetables and more than 40 percent of their fruits.
The study, which appears in the current issue of The Journal ...
MRI scans show structural brain changes in people at risk for Alzheimer's disease
2010-11-17
(CHICAGO) – New results from a study by neuroscientists at Rush University Medical Center suggest that people at risk of developing Alzheimer's disease exhibit a specific structural change in the brain that can be visualized by brain imaging. The findings may help identify those who would most benefit from early intervention.
The study will be presented at Neuroscience 2010, the annual meeting for the Society of Neuroscience in San Diego, Calif., on Wednesday, November 17.
"One of the main challenges in the field of Alzheimer's disease is identifying individuals at ...
Astronomers discover merging star systems that might explode
2010-11-17
VIDEO:
The binary star system J0923+3028 consists of two white dwarfs that are gradually spiraling in toward each other. In about 100 million years they will merge. Since their combined mass...
Click here for more information.
Sometimes when you're looking for one thing, you find something completely different and unexpected. In the scientific endeavor, such serendipity can lead to new discoveries. Today, researchers who found the first hypervelocity stars escaping the ...
Never-smokers fare far better than smokers after radiation therapy for head and neck cancer
2010-11-17
(SACRAMENTO, Calif.) — Patients with head and neck cancer who have never smoked have much better survival rates after radiation therapy than patients with a history of smoking, new research from UC Davis Cancer Center has found.
The study by Allen M. Chen and colleagues in the UC Davis radiation oncology and otolaryngology departments is among the first of its kind to examine prognosis differences based on smoking history in patients with head and neck cancer who are treated with radiation therapy.
The study, published online in American Journal of Clinical Oncology, ...
Your view of personal goals can affect your relationships
2010-11-17
How you think about your goals—whether it's to improve yourself or to do better than others—can affect whether you reach those goals. Different kinds of goals can also have distinct effects on your relationships with people around you, according to the authors of a paper published in Current Directions in Psychological Science, a journal of the Association for Psychological Science.
People with "mastery goals" want to improve themselves. Maybe they want to get better grades, make more sales, or land that triple toe loop. On the other hand, people with what psychologists ...
Hearing colors, seeing sounds: New research explores sensory overlap in the brain
2010-11-17
SAN DIEGO — New research indicates that the integration of senses and functions in the brain is common. About two percent of the population has a condition called synesthesia, in which two different sensations, like color and sound, are experienced at once. Although this condition is rare, the new findings suggest the brain is wired in complex and sometimes overlapping ways to help people interpret and understand their environments. The research was presented at Neuroscience 2010, the annual meeting of the Society for Neuroscience and the world's largest source of emerging ...
Princeton scientist recasts problems, offering new tools for old quandaries
2010-11-17
A Princeton scientist with an interdisciplinary bent has taken two well-known problems in mathematics and reformulated them as a physics question, offering new tools to solve challenges relevant to a host of subjects ranging from improving data compression to detecting gravitational waves.
Salvatore Torquato, a professor of chemistry, has shown that two abstract puzzles in geometry -- known as the "covering" and "quantizer" problems -- can be recast as "ground state" problems in physics. Ground state problems relate to the study of molecule systems at their lowest levels ...
Bioengineers provide adult stem cells with simultaneous chemical, electrical and mechanical cues
2010-11-17
Bioengineers from the University of California, San Diego have achieved the "Triple Crown" of stem cell culture – they created an artificial environment for stem cells that simultaneously provides the chemical, mechanical and electrical cues necessary for stem cell growth and differentiation. Building better microenvironments for nurturing stem cells is critical for realizing the promises of stem-cell-based regenerative medicine, including cartilage for joint repair, cardiac cells for damaged hearts, and healthy skeletal myoblasts for muscular dystrophy patients. The advance ...
Communication engages complex brain circuitry and processes
2010-11-17
SAN DIEGO — New human and animal studies released today uncover the extensive brain wiring used in communication and provide new insights into how the brain processes and produces language, accents, and sounds. The research also explores the brain abnormalities in people with speech and language problems, such as stuttering, suggesting future treatment avenues. The new findings were presented at Neuroscience 2010, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news on brain science and health.
Communication involves a complex ...
New ways to detect and treat Alzheimer's disease
2010-11-17
SAN DIEGO — New studies identify brain changes in people with Alzheimer's disease. The results give researchers a greater understanding of the disease and may help at-risk individuals by improving early detection. New animal research also shows a novel approach to Alzheimer's vaccine design that may avoid dangerous side effects. These new results were reported at Neuroscience 2010, the annual meeting of the Society for Neuroscience and the world's largest source of emerging news on brain science and health.
About 5.3 million people have Alzheimer's disease, according ...