|
E-mail this page to a friend!
Senior Citizen Health & Medicine
How Switch Regulates Fat, Cholesterol Production
Revealed by Researchers
Could lead to treatments for metabolic syndrome -
common in senior citizens
 August 3, 2006 There is a molecular switch that
regulates fat and cholesterol production, and researchers think they
have discovered how it works. Excess intake of food, along with lack of
exercise, appears to keep the switch in "on." Their discovery may help
advance treatments for metabolic syndrome, the constellation of diseases
that includes high cholesterol, obesity, type II diabetes, and high
blood pressure. It is most common among older people after they reach
age 60.
| |
Related Stories |
|
| |
Obese Metabolic Syndrome Patients Lower Heart
Disease Risk 20 Percent
Multidisciplinary approach found by obesity
researchers
April 28, 2006 - Obesity researchers at the Medical
College of Wisconsin in Milwaukee found that a multidisciplinary
clinical approach to caring for obese patients with metabolic syndrome
(the presence of usually three or more factors, such as high blood
pressure, abdominal obesity, high triglyceride levels, low HDL levels,
and high fasting levels of blood sugar) could swiftly and significantly
lower their risk for heart disease.
Read more...
Senior Citizens Reduce Cardiovascular, Diabetes
Risks Eating More Whole Grains
Feb. 6, 2006 Senior citizens can lower their risk
of cardiovascular disease and reduce the threat of metabolic syndrome by
consuming a diet rich in whole-grain foods. Metabolic syndrome is a
collection of risk factors that puts people at an increased risk of
cardiovascular disease and type 2 diabetes.
Read
more...
Older Americans Leading in the War Against Obesity
Overweight Rising
for children, teens, men and steady for women
April
5, 2006 - A new study published today in the Journal of the American
Medical Society headlined news that overweight and obesity continues to
climb for children and men, while it holds steady for women, but in the
same time comparison - 1999 to 2004 - older Americans (60 and over)
appear to be leading the way in the fight against fat.
Read more...
Senior Citizens Among the Least Interested in Losing
Weight
Most Americans want to lose weight but only 43% of
older men
March
10, 2006 Surgeon General Richard Carmona last week issued dire
warnings about overweight Americans, saying the threat from obesity
"will dwarf 9-11." His alarm may not have been heard by many senior
citizens, who are among the least likely to be interested in losing
weight. The only group, in fact, less interested in losing weight than
senior men or young men between the ages of 18 and 29, according to a
new Gallup Poll. Read
more...
Read more
on
Health & Medicine |
|
The study by researchers at Harvard Medical School
and Massachusetts General Hospital is now published in the online
version of the scientific journal Nature and will appear in the August
10th print edition.
"We have identified a key protein that acts
together with a family of molecular switches to turn on cholesterol and
fat (or lipid) production," says principal investigator Anders Nδδr,
PhD, assistant professor of cell biology at Harvard Medical School and
the Massachusetts General Hospital Cancer Center.
"The identification of this protein interaction and
the nature of the molecular interface may one day allow us to pursue a
more comprehensive approach to the treatment of metabolic syndrome."
High levels of cholesterol and lipids are linked to
a number of interrelated medical conditions and diseases, including
obesity, type II diabetes, fatty liver, and high blood pressure. This
set of conditions and diseases, known as metabolic syndrome, are
afflicting a rapidly increasing portion of society and serve as a major
risk factor for heart disease, the leading cause of death in the
developed world.
| |
About Metabolic Syndrome |
|
| |
Read what the Mayo Clinic says about metabolic
syndrome below news report. |
|
Treatments for diseases associated with metabolic
syndrome have focused primarily on individual elements, such as high
LDL-cholesterol (targeted by the cholesterol-lowering statin drugs).
However, more effective ways to treat all of the components of metabolic
syndrome are needed. One attractive approach might be to target the
genetic switches that promote cholesterol and lipid synthesis, but it
would require a detailed understanding of the regulatory mechanisms
before drug targets can be identified.
After eating a meal, a family of proteins act as
switches to turn on cholesterol and fat (or lipid) production. This
family of proteins is known as SREBPs, or sterol regulatory element
binding proteins. Between meals, the production of cholesterol and
lipids should be turned off, however, excess intake of foods, coupled
with lack of exercise, appear to disturb the normal checks and balances
that control SREBPs, resulting in overproduction of cholesterol and
lipids.
In the Nature paper, the HMS and MGH Cancer Center
team has shown that a protein called ARC105, which binds to SREBPs, is
essential in controlling the activity of the SREBP family of proteins.
"ARC105 represents a lynchpin for SREBPs control of cholesterol and
lipid biosynthesis genes, which may provide a potential molecular
Achilles heel that could be targeted by drugs" says Dr. Nδδr.
The researchers initially found that after removing
ARC105 from human cells by a process called RNAi, SREBPs were no longer
able to activate cholesterol and lipid biosynthesis genes. To validate
these findings in a physiological setting, the researchers turned to the
microscopic worm C. elegans, a favorite model organism among those
studying evolutionarily conserved biological processes because of its
rapid generation time and relative simplicity of genetics, and which had
previously been used to study mechanisms of fat regulation.
Through a collaborative effort with the worm
genetics group of Anne Hart, PhD, HMS associate professor of pathology
at the MGH Cancer Center, the team demonstrated that the C. elegans
homologues of SREBP and ARC105, known as SBP-1 and MDT-15, respectively,
are necessary for production and storage of fat. The worms had regular
fat production when SBP-1 and MDT-15 functioned normally, but when
researchers used RNAi to knock out function of either SBP-1 or MDT-15,
the worms lost their ability to properly store fat, lay eggs, and move
normally.
"The striking effects of the RNAi knock downs in C.
elegans suggest that the ARC105/SREBP pathway may play a key role in
lipid production in humans," said Laurie Tompkins, PhD, of the National
Institute of General Medical Sciences, which partially supported the
research. "This work highlights the value of model organisms in helping
us understand cellular processes that impact human health."
The research team also showed that removal of
ARC105 in human cells by RNAi also negatively affects the same key SREBP
target gene as identified in C. elegans. This suggests that the
molecular switch is evolutionarily conserved (and therefore likely
physiologically important).
Exhaustive biochemical detective work performed by
the Nδδr group together with the group of Gerhard Wagner, PhD, HMS
professor in the Department of Biological Chemistry and Molecular
Pharmacology, identified exactly how SREBP and ARC105 interact. They
found a flexible tail on the SREBP molecule that fits into a specific
groove on a region of ARC105 called KIX.
The researchers analyzed the amino acid sequence of
the ARC105 protein, testing many different sections using NMR
spectroscopy to eventually find the KIX area--just one tenth the area of
the larger ARC105 protein--that specifically binds to SREBP. This
specific interaction between SREBP and ARC105 might be a target for
small molecule drugs, according to Dr. Wagner.
"While RNAi completely knocks out a protein
including its other functions, perhaps not related to fat metabolism, a
small molecule is a more subtle tool that could eliminate one
protein-to-protein interaction," says Dr. Wagner. Finding a molecule
that attaches to and inhibits the flexible tail of SREBP is unlikely,
but a search for inhibitors to fit the grooved KIX site looks much more
promising.
The team is already initiating high-throughput
screening at Harvard Medical School's Institute of Chemistry and Cell
Biology to identify small molecule inhibitors of the KIX site.
"Of course there are numerous hurdles that would
need to be overcome before finding specific and effective treatments
based on these findings," says Dr. Nδδr. If small molecules that
specifically interfere with the interaction of SREBPs and ARC105 could
be identified, careful studies in human cells and in mice would be
needed to verify the specificity and efficacy in repressing cholesterol
and fat production.
"Unforeseen side effects of such small molecules in
mouse studies or in human clinical trials could also emerge, prohibiting
further follow-up", cautions Dr. Nδδr.
Notes on Study:
The National Institutes of Health, the Damon
Runyon Cancer Research Foundation, and the Milton Foundation of Harvard
University supported the study.
Harvard Medical School
http://hms.harvard.edu/
Harvard Medical School has more than 7,000 full-time faculty working in
10 academic departments housed on the School's Boston quadrangle or in
one of 48 academic departments at 18 Harvard teaching hospitals and
research institutes. Those Harvard hospitals and research institutions
include Beth Israel Deaconess Medical Center, Brigham and Women's
Hospital, Cambridge Health Alliance, The CBR Institute for Biomedical
Research, Children's Hospital Boston, Dana-Farber Cancer Institute,
Forsyth Institute, Harvard Pilgrim Health Care, Joslin Diabetes Center,
Judge Baker Children's Center, Massachusetts Eye and Ear Infirmary,
Massachusetts General Hospital, Massachusetts Mental Health Center,
McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute,
Spaulding Rehabilitation Hospital, and the VA Boston Healthcare System.
Massachusetts General Hospital
http://www.mgh.harvard.edu/
Massachusetts General Hospital, established in 1811, is the original and
largest teaching hospital of Harvard Medical School. The MGH conducts
the largest hospital-based research program in the United States, with
an annual research budget of nearly $500 million and major research
centers in AIDS, cardiovascular research, cancer, computational and
integrative biology, cutaneous biology, human genetics, medical imaging,
neurodegenerative disorders, regenerative medicine, transplantation
biology and photomedicine. MGH and Brigham and Women's Hospital are
founding members of Partners HealthCare HealthCare System, a
Boston-based integrated health care delivery system.
Mayo Clinic on Metabolic Syndrome
Metabolic syndrome is a cluster of conditions that
occur together, increasing your risk for heart disease, stroke and
diabetes. Having just one of these conditions increased blood
pressure, elevated insulin levels, excess body fat around the waist or
abnormal cholesterol levels contributes to your risk of serious
disease. In combination, your risk is even greater.
Research into the complex underlying process
linking this group of conditions is ongoing. As the name suggests,
metabolic syndrome is tied to the bodys metabolism, possibly to a
condition called insulin resistance.
Not all experts agree on the definition of
metabolic syndrome or whether it even exists as a distinct medical
condition. Doctors have talked about this constellation of risk factors
for years and have called it many names, including syndrome X and
insulin resistance syndrome. Whatever its called, and however its
precisely defined, this collection of risk factors is apparently
becoming more prevalent.
If you have metabolic syndrome or any of its
components, you have the opportunity to make aggressive lifestyle
changes that can delay or derail the development of serious diseases.
Risk factors
The following factors increase your chances of
having metabolic syndrome:
● Age. The prevalence of metabolic syndrome
increases with age, affecting less than 10 percent of people in their
20s and 40 percent of people in their 60s. However, one study shows that
about one in eight schoolchildren have three or more components of
metabolic syndrome.
● Race. Hispanics and Asians seem to be at
greater risk for metabolic syndrome than other races are.
● Obesity. A body mass index (BMI) a measure of
your percentage of body fat based on height and weight greater than 25
increases your risk of metabolic syndrome. So does abdominal obesity
having an apple shape rather than a pear shape.
● History of diabetes. You're more likely to have
metabolic syndrome if you have a family history of type 2 diabetes or a
history of diabetes during pregnancy (gestational diabetes).
● Other diseases. A diagnosis of high blood
pressure, cardiovascular disease or polycystic ovary syndrome a
similar type of metabolic problem that affects a woman's hormones and
reproductive system also increases the risk of metabolic syndrome.
>> Click to more information from Mayo Clinic.
Click to More Senior News on the
Front Page
Copyright: SeniorJournal.com |
