[PHNUTR-L] First link found between obesity, inflammation and vascular disease

[Kathrynne Holden, MS, RD]

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Public release date: 16-Sep-2005
http://www.eurekalert.org/pub_releases/2005-09/uoth-flf091605.php

Contact: Scott Merville
scott.merville at uth.tmc.edu
713-500-3042
University of Texas Health Science Center at Houston

Julie Penne
jpenne at mdanderson.org
713-792-0655
University of Texas M. D. Anderson Cancer Center

First link found between obesity, inflammation and vascular disease

Researchers find human fat cells produce C-reactive protein

HOUSTON (Sept. 16, 2005) - Researchers at The University of Texas M. D. 
Anderson Cancer Center and The University of Texas Health Science Center 
at Houston have found that human fat cells produce a protein that is 
linked to both inflammation and an increased risk of heart disease and 
stroke.

They say the discovery, reported in Journal of the American College of 
Cardiology, goes a long way to explain why people who are overweight 
generally have higher levels of the molecule, known as C-reactive 
protein (CRP), which is now used diagnostically to predict future 
cardiovascular events.

And they also report some good news: the researchers found that aspirin 
and statin drugs, now commonly used to treat heart diseases, effectively 
damp down production of CRP from fat cells.

"This study is the first to show how body fat participates in the 
inflammatory process that leads to cardiovascular disease, but also 
demonstrates that this process can be blocked by drugs now on the 
market," said study leader Edward T. H. Yeh, M.D., who is both chairman 
of the Department of Cardiology at M. D. Anderson and director of the 
Research Center for Cardiovascular Disease at the Brown Foundation 
Institute of Molecular Medicine for the Prevention of Human Diseases at 
the UT Health Science Center at Houston.

UT Health Science Center at Houston President James T. Willerson, M.D., 
is a co-author of the study.

Adipose tissue (body fat) has been lately regarded as a separate body 
organ which can produce a number of different biologically active 
molecules - such as cytokine proteins that are associated with 
inflammation, and the hormone resistin, which is linked to insulin 
resistance and the development of type two diabetes.

Even if they are healthy, people with more adipose tissue also tend to 
have higher levels of CRP. Previous research, however, had only found 
CRP to be produced in liver tissue, although Yeh, Willerson and Paolo 
Calabro, M.D., discovered in 2003 that the protein also is manufactured 
in the walls of blood vessels.

"But that didn't explain obesity's connection to high levels of CRP and 
it also was not clear why CRP is higher in patients who have metabolic 
disorders," Yeh said.

So the research team decided to see whether fat cells themselves can be 
stimulated by inflammatory cytokines or resistin to produce CRP. To help 
find out, plastic surgery patients at M. D. Anderson donated adipose 
tissue that would have been discarded, and the research team then 
isolated fat cells, cultured them and stimulated them under a number of 
different conditions. They found the cells produced cytokines that 
resulted in inflammation and that this process triggered production of 
high levels of C-reactive proteins.

The researchers also discovered that resistin, the hormone associated 
with diabetes and insulin resistance, can stimulate production of CRP 
proteins. "And this is interesting because it is known that resistin is 
itself produced by fat cells," Yeh said.

"We know that patients with metabolic syndromes have higher levels of 
CRPs, as well as a higher risk of developing heart disease and stroke, 
but no one understands why that is," Yeh said. "If fat cells by 
themselves produce inflammatory signals that trigger cells to produce 
CRPs, and if CRPs also produce biological effects on vascular walls, 
that could explain the higher risk of cardiovascular disease."

The investigators then solved the other part of the puzzle – why it is 
that aspirin, statin drugs and an agent known as troglitazone, used to 
treat diabetes, can reduce CRP levels. They exposed the cultured fat 
cells that were producing high levels of CRPs to these drugs, and found 
production of the proteins declined. "We knew from studying patients 
that these drugs can reduce C-reactive proteins, but now we have direct 
proof of their benefit."

Even as the CRP picture becomes clearer, there is still much that is not 
known, say the researchers, including the reason why fat tissue produces 
an inflammatory response, and just precisely how CRP participates in 
that process.

"Inflammation is a very complicated phenomenon, but at least we now have 
a few more clues as to what it does and how the damage it produces can 
be prevented," Yeh noted.
###
Co-authors include Calabro, an Italian cardiology fellow at the UT 
Health Science Center at Houston, and David Chang, M.D., a plastic 
surgeon at M. D. Anderson Cancer Center. Co-author Willerson also is 
president-elect, medical director and director of research for the Texas 
Heart Institute at St. Luke's Episcopal Hospital.
-- 
Kathrynne Holden, MS, RD < fivestar at nutritionucanlivewith.com >
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