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First Link Found Between Obesity, Inflammation And Vascular Disease

Date:
September 17, 2005
Source:
University of Texas Health Science Center at Houston
Summary:
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.
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HOUSTON (Sept. 16, 2005) - Researchers at The University of Texas M. D.Anderson Cancer Center and The University of Texas Health ScienceCenter at Houston have found that human fat cells produce a proteinthat is linked to both inflammation and an increased risk of heartdisease and stroke.

They say the discovery, reported in Journal of the American Collegeof Cardiology, goes a long way to explain why people who are overweightgenerally have higher levels of the molecule, known as C-reactiveprotein (CRP), which is now used diagnostically to predict futurecardiovascular events.

And they also report some good news: the researchers found that aspirinand 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 theinflammatory process that leads to cardiovascular disease, but alsodemonstrates that this process can be blocked by drugs now on themarket," said study leader Edward T. H. Yeh, M.D., who is both chairmanof the Department of Cardiology at M. D. Anderson and director of theResearch Center for Cardiovascular Disease at the Brown FoundationInstitute of Molecular Medicine for the Prevention of Human Diseases atthe 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 bodyorgan which can produce a number of different biologically activemolecules - such as cytokine proteins that are associated withinflammation, and the hormone resistin, which is linked to insulinresistance and the development of type two diabetes.

Even if they are healthy, people with more adipose tissue alsotend to have higher levels of CRP. Previous research, however, had onlyfound CRP to be produced in liver tissue, although Yeh, Willerson andPaolo Calabro, M.D., discovered in 2003 that the protein also ismanufactured in the walls of blood vessels.

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

So the research team decided to see whether fat cells themselves can bestimulated by inflammatory cytokines or resistin to produce CRP. Tohelp find out, plastic surgery patients at M. D. Anderson donatedadipose tissue that would have been discarded, and the research teamthen isolated fat cells, cultured them and stimulated them under anumber of different conditions. They found the cells produced cytokinesthat resulted in inflammation and that this process triggeredproduction of high levels of C-reactive proteins.

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

"We know that patients with metabolic syndromes have higher levels ofCRPs, as well as a higher risk of developing heart disease and stroke,but no one understands why that is," Yeh said. "If fat cells bythemselves produce inflammatory signals that trigger cells to produceCRPs, 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 isthat aspirin, statin drugs and an agent known as troglitazone, used totreat diabetes, can reduce CRP levels. They exposed the cultured fatcells that were producing high levels of CRPs to these drugs, and foundproduction of the proteins declined. "We knew from studying patientsthat these drugs can reduce C-reactive proteins, but now we have directproof of their benefit."

Even as the CRP picture becomes clearer, there is still much that isnot known, say the researchers, including the reason why fat tissueproduces an inflammatory response, and just precisely how CRPparticipates in that process.

"Inflammation is a very complicated phenomenon, but at least we nowhave a few more clues as to what it does and how the damage it producescan be prevented," Yeh noted.

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Co-authors include Calabro, an Italian cardiology fellow at the UTHealth Science Center at Houston, and David Chang, M.D., a plasticsurgeon at M. D. Anderson Cancer Center. Co-author Willerson also ispresident-elect, medical director and director of research for theTexas Heart Institute at St. Luke's Episcopal Hospital.


Story Source:

The above story is based on materials provided by University of Texas Health Science Center at Houston. Note: Materials may be edited for content and length.


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University of Texas Health Science Center at Houston. "First Link Found Between Obesity, Inflammation And Vascular Disease." ScienceDaily. ScienceDaily, 17 September 2005. <www.sciencedaily.com/releases/2005/09/050917085024.htm>.
University of Texas Health Science Center at Houston. (2005, September 17). First Link Found Between Obesity, Inflammation And Vascular Disease. ScienceDaily. Retrieved May 27, 2015 from www.sciencedaily.com/releases/2005/09/050917085024.htm
University of Texas Health Science Center at Houston. "First Link Found Between Obesity, Inflammation And Vascular Disease." ScienceDaily. www.sciencedaily.com/releases/2005/09/050917085024.htm (accessed May 27, 2015).

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