Newswise — Why does extra fat around the
waist increase the risk of heart disease? A new study by Wake Forest
University Baptist Medical Center researchers and colleagues
suggests that inflammation may be the key.
“It is well known that obesity
affects nearly one-third of adults in the United States and is
closely linked with heart disease,” said Tongjian You, Ph.D.,
instructor in geriatric medicine at Wake Forest Baptist and lead
author. “While we don’t fully understand the link between obesity
and heart disease, our study suggests that inflammatory proteins
produced by fat itself may play a role.”
The study, to be published in the
April issue of the American Journal of Physiology – Endocrinology
and Metabolism, evaluated whether inflammatory proteins produced
by fat are linked to risk factors for heart disease, including high
blood pressure, high cholesterol and how the body responds to
insulin. The research is based on a new idea in medicine – that fat
is an “organ” that produces proteins and hormones that affect
metabolism and health.
The researchers studied two
proteins that promote inflammation (interleukin 6 and tumor necrosis
factor alpha) and a protein that promotes blood clots (plasminogen
activator inhibitor 1). These proteins are all manufactured by fat
tissue and involved in atherosclerosis, the buildup of fatty
deposits in the linings of blood vessels. In addition, the
scientists also looked at two “good” proteins, leptin, which
regulates energy metabolism, and adiponectin, which has
anti-inflammatory effects.
To gauge production levels of the
proteins, the scientists took small samples of subcutaneous fat,
which is just under the skin, from the abdomen and measured levels
of messenger RNA (mRNA), which carries the genetic code instructions
for cells to create the proteins.
The study included 20
post-menopausal women from 50 to 70 years old who were overweight or
obese and had waists larger than 35 inches. Women in this age group
are at increased risk for metabolic syndrome, a cluster of symptoms
that increases the risk for heart disease. The syndrome is diagnosed
when someone has at least three of the following: abdominal obesity,
high triglycerides, low levels of high-density liprorotein (“good”)
cholesterol, high blood pressure and increased levels of glucose
(sugar) in the blood.
In 15 study participants without
diabetes, higher levels of the “bad” proteins, interleukin 6 and
tumor necrosis factor alpha, were associated with a lower ability to
respond to insulin and use glucose. On the other hand, higher levels
of the “good” protein adiponectin were associated with an increased
ability to use glucose. Eight women who were diagnosed with
metabolic syndrome – and had multiple risk factors for heart disease
– had levels of adiponectin that were 32 percent lower than the 12
women who didn’t have the disorder.
“This suggests that low production
of adiponectin in subcutaneous fat is linked with an elevated risk
of heart disease,” said You.
The findings are significant
because of the prevalence of both heart disease and obesity in the
United States. Heart disease is the No. 1 killer in the United
States, causing about 79,000 more deaths per year than the next five
leading causes of death combined.
“It’s possible that modifying the
inflammatory proteins through medication could also lower the risk
of heart disease,” said Barbara Nicklas, Ph.D., senior researcher
and an associate professor of internal medicine. “The findings point
to a possible treatment target for new drugs. Our goal is to learn
more about how these proteins are produced and how levels can be
changed.”
Nicklas and colleagues have
already begun a study to test whether diet and exercise will affects
levels of the proteins. Scientists already know that weight loss and
physical activity can reduce inflammation, but don’t know if this
happens because the production of inflammatory proteins by fat
tissue is reduced.
“We need to understand more about
the mechanism,” Nicklas said.
The research was supported by the
National Institutes of Health, the Wake Forest University Claude D.
Pepper Older Americans Independence Center and the Wake Forest
University General Clinical Research Center. Other researchers were
Rongze Yang, Ph.D., and Dawei Gong, from the University of Maryland
School of Medicine, and Mary Lyles, M.D., from Wake Forest Baptist.
About Wake Forest University
Baptist Medical Center: Wake Forest Baptist is an academic health
system comprised of North Carolina Baptist Hospital and Wake Forest
University Health Sciences, which operates the university’s School
of Medicine. The system comprises 1,282 acute care, psychiatric,
rehabilitation and long-term care beds and is consistently ranked as
one of “America’s Best Hospitals” by U.S. News & World Report.
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