First Link Found Between Body Fat and Inflammation

September 22, 2005

Researchers have found that human fat cells produce a protein that is

linked to inflammation.

Link and full text:

http://www.docguide.com/news/content.nsf/news/8525697700573E188525707E00741AF8

First Link Found Between Obesity, Inflammation and Vascular Disease

Researchers find human fat cells produce C-reactive protein

HOUSTON, TX -- September 16, 2005 -- Researchers at The University of

Texas M.D. 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 T. H. Yeh, MD, who is both chairman

of the Department of Cardiology at M.D. 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 T. Willerson, MD,

is a co-author of the study.

Adipose tissue has been lately regarded as a separate body organ that

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 Drs. Yeh, Willerson and

Paolo Calabro, MD, 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, " Dr. Yeh said.

So the research team decided to see whether fat cells themselves could

be stimulated by inflammatory cytokines or resistin to produce CRP. To

help find out, plastic surgery patients at M.D. 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, could stimulate production of

CRP proteins. " And this is interesting because it is known that

resistin is itself produced by fat cells, " Dr. 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, the researchers say, 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, " Dr. Yeh noted.

Co-authors include Calabro, an Italian cardiology fellow at the UT

Health Science Center at Houston, and Chang, MD, a plastic

surgeon at M. D. 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.

SOURCE: The University of Texas Health Science Center at Houston

September 22, 2005

Very interesting Dave; here's a bit more relating adipose to ;ow level

inflammation in NON-OBESE HEALTHY individuals:

1)Body fat and C-reactive protein levels in healthy non-obese men.

Bo M, Raspo S, Morra F, Isaia G, Cassader M, Fabris F, Poli L.

University of Turin, Department of Medical and Surgical Disciplines,

Geriatrics Section, Torino, Italy. mario.bo@...

BACKGROUND AND AIM: The relationships between C-reactive protein (CRP)

levels, adipose tissue and metabolic alterations have not been clearly

established in healthy non-obese subjects. We investigated the

relationships between body fat, CRP levels and metabolic variables in

healthy, non-obese sons of patients affected by metabolic syndrome

(MS). METHODS AND RESULTS: Age, CRP and interleukin 6 (IL-6) levels,

anthropometric measures (body mass index, BMI; waist circumference and

waist-to-hip ratio, WHR), total and regional fat content (as

determined by means of dual X-ray absorptiometry, DXA), total and LDL

cholesterol, and the metabolic variables related to MS

(HDL-cholesterol, triglyceride, glucose and insulin levels; the

fasting insulin resistance index, FIRI; blood pressure) were evaluated

in 85 healthy non-obese sons of MS patients. Linear and multiple

regression analyses were used to evaluate the relationships between

body fat, metabolic variables and CRP levels, and to investigate

whether the association between body fat content and metabolic

variables persists after adjustment for CRP levels. Body fat was

associated with all of the investigated variables. CRP levels were

associated with total and regional body fat, the anthropometric index

of weight, age, and with some metabolic alterations (HDL-cholesterol

and triglyceride levels, systolic blood pressure, and fasting insulin

and LDL-cholesterol levels). The associations between total body fat

and the metabolic variables did not change after adjustment for CRP

levels. Total body fat was the best predictor of CRP levels

(p<0.0001). CONCLUSIONS: In healthy, non-obese sons of MS patients,

total body fat is the best predictor of CRP levels, and remains

closely associated with metabolic abnormalities after adjustment for

CRP levels. These findings strongly support the hypothesis that body

fat is the main determinant of metabolic abnormalities and a low

inflammatory state, at least in healthy subjects.

PMID: 15242238

2)Metabolism. 2004 Aug;53(8):984-8. Related Articles, Links

Click here to read

Body fat is the main predictor of fibrinogen levels in healthy

non-obese men.

Bo M, Raspo S, Morra F, Cassader M, Isaia G, Poli L.

Azienda Ospedaliera San Giovanni Battista, Department of Medical

and Surgical Disciplines, University of Turin, Italy.

Previous studies have demonstrated that circulating levels of

C-reactive protein (CRP), a marker of cardiovascular risk, are

strictly related to body fatness. Elevated fibrinogen levels are also

predictive of future cardiovascular events. The metabolic background

of this relationship and the predictors of fibrinogen levels have not

been well established. We aimed to evaluate whether fibrinogen levels

are associated with body fat content and distribution and to determine

the independent predictors of fibrinogen levels in a sample of

healthy, non-obese, nonsmoking young adult men. Age, anthropometric

measures (body mass index [bMI], waist-to-hip ratio [WHR]), total and

regional fat content (determined by dual x-ray absorptiometry [DXA]),

metabolic variables (total cholesterol [T-Chol], low-density

lipoprotein cholesterol [LDL-C], and high-density lipoprotein

cholesterol [HDL-C]; triglycerides [TG]; glucose and insulin levels;

fasting insulin resistance index [FIRI]; blood pressure),

interleukin-6 (IL-6), and acute-phase reactants levels (fibrinogen,

highly sensitive [hs]-CRP) were determined in 87 healthy nonsmoking,

non-obese subjects. Linear regression analysis was used to evaluate

the association between body fat, fibrinogen, and metabolic variables,

and multiple regression model analysis was used to examine the

independent predictors of fibrinogen levels. Eighty-seven (30.5 +/-

3.5 years) non-obese (mean BMI 24.1 +/- 3.5) men were studied.

Fibrinogen levels were strongly associated with measures of body fat

and with metabolic variables. Total body fat (P < .0001) and

LDL-cholesterol (P < .01) were the independent predictors of

fibrinogen levels, accounting for 29.5% and 10.9% of its variance,

respectively. Total body fat was the best independent predictor of

hs-CRP levels, accounting for 32.5 % of its variance. We conclude that

in healthy, non-obese subjects, body fat content is the main predictor

of fibrinogen levels, as well of hs-CRP levels. These findings support

the speculation that there is a direct mechanism by which adipose

tissue might regulate the levels of circulating acute-phase reactants.

> Researchers have found that human fat cells produce a protein that is

> linked to inflammation.

>

> Link and full text:

>

http://www.docguide.com/news/content.nsf/news/8525697700573E188525707E00741AF8

>

> First Link Found Between Obesity, Inflammation and Vascular Disease

>

> Researchers find human fat cells produce C-reactive protein

>

> HOUSTON, TX -- September 16, 2005 -- Researchers at The University of

> Texas M.D. 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 T. H. Yeh, MD, who is both chairman

> of the Department of Cardiology at M.D. 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 T. Willerson, MD,

> is a co-author of the study.

>

> Adipose tissue has been lately regarded as a separate body organ that

> 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 Drs. Yeh, Willerson and

> Paolo Calabro, MD, 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, " Dr. Yeh said.

>

> So the research team decided to see whether fat cells themselves could

> be stimulated by inflammatory cytokines or resistin to produce CRP. To

> help find out, plastic surgery patients at M.D. 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, could stimulate production of

> CRP proteins. " And this is interesting because it is known that

> resistin is itself produced by fat cells, " Dr. 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, the researchers say, 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, " Dr. Yeh noted.

>

> Co-authors include Calabro, an Italian cardiology fellow at the UT

> Health Science Center at Houston, and Chang, MD, a plastic

> surgeon at M. D. 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.

>

> SOURCE: The University of Texas Health Science Center at Houston

September 22, 2005