Far-reaching effects of fat article

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Far-reaching effects of fat

Scientists think chemicals from fat tissue damage many body processes

By SARAH AVERY, Staff Writer

http://www.newsobserver.com/news/health_science/story/2462837p-8866896c.html

Fat, once simply considered unsightly flab, is not as inert as

everyone thought. It is very much alive.

And it's playing an active role in diseases, from diabetes to heart

trouble, changing the way scientists approach the study of obesity and

its attending illnesses.

" Fat may be controlling a lot of things, " said Barbara Nicklas, a

senior researcher at Wake Forest University Baptist Medical Center in

Winston-Salem. " About every month, there's a new factor that somebody

has found to be expressed and secreted by [fat] tissue. "

This spring, Nicklas and a team of researchers at Wake Forest and the

University of land described how abdominal fat actually makes

inflammatory proteins that increase the risk for heart disease.

The Wake Forest study examined 20 post-menopausal women who were

overweight or obese. Some of them had the precursor symptoms of heart

disease and diabetes, and others didn't.

" We wanted to know if there was something about that person's fat

making them sick, " Nicklas said.

The researchers found that the women with the precursor disease,

called metabolic syndrome, had higher levels of inflammatory proteins

in their blood.

They are now studying whether diet and exercise could reduce the

inflammatory proteins, and thereby reduce the risk for heart disease.

But the larger mystery is why the fat tissue in some overweight people

creates more problems than in others.

" It could be genetic; it could be nutritional. ... It's hard to say, "

Nicklas said.

Fat's leading role

The Wake Forest work adds to a growing body of evidence that fat,

especially the " spare tire " variety around the middle, is a highly

complex substance that works like an organ. It secretes hormones into

the blood. It regulates metabolism. It even influences the immune system.

" Fat has a lot to say about what the rest of the body is doing, " said

Newgard, director of the W. Stedman Nutrition and

Metabolism Center at Duke University Medical Center.

That line of thinking represents a relatively new approach to a major

problem, with six in 10 Americans considered overweight or obese. It

was ushered in with the discovery in the 1990s that fat produces a

hormone known as leptin, which acts on receptors in the brain,

shutting down the urge to eat.

The hormone was hailed as a potential cure for obesity, but a leptin

drug did not produce marked weight loss as hoped.

Newgard said the leptin discovery showed that obesity is not a simple

matter. What first appeared to be a hormone deficiency might have a

more complicated cause, because many obese people have a lot of leptin

circulating in the blood. That suggests the problem might stem from a

resistance to leptin.

" Somehow the brain is not hearing the signal, " Newgard said.

Other hormones secreted by fat suggest similarly complex interactions.

Two proteins -- adiponectin and resistin -- have been found to

regulate insulin sensitivity, providing a direct link between fat and

the development of type 2 diabetes, by far the most prevalent form of

that disease.

Two other proteins made by fat contribute to the buildup of fatty

deposits in the lining of blood vessels, leading to heart disease. Fat

also produces cytokines, which can stimulate or inhibit the immune system.

" There's a lot of extremely exciting research at the molecular level

that is trying to understand how the tissues correspond to each

other, " said Dr. H.A. Barakat, a researcher at East Carolina

University who is exploring differences in metabolism between white

and African-American women. " It's a very beautiful time to be in

research now. "

The lifestyle factor

The growing realization about fat is also fueling a new appreciation

for the role of diet and exercise as cures. The Wake Forest team is

continuing to examine how the overweight women in its study have

responded, on a molecular level, to diet and exercise.

At Duke, Newgard's group is testing eight regimens, and whether they

alter the hormonal secretions of fat. One of the problems, Newgard

said, is that fat almost seems to self-perpetuate, sending signals

that make people eat more -- and make more fat.

" We're beginning to appreciate that fat tissue has ways of signaling

its own status to the rest of the body, and those signals come by the

production of hormones that change feeding behavior or change energy

balance, " Newgard said. " They have important body-wide effects on fuel

metabolism. "

That comes as no surprise to Martha E. Myrick, who participated in the

study at Wake Forest. She said her weight had gone up and down by 20

pounds for several years.

" Once you gain weight and start losing, and gain it back, it gets

harder and harder to lose it, " said Myrick, a retired nurse in

Winston-Salem. As part of her participation in the study, she was put

on a diet and exercise plan that helped her lose the extra weight.

Now a year later, she credits the regimen with improving her physical

condition, enabling her to mount a recent battle with breast cancer.

And she wonders whether carrying the excess weight might have had

something to do with her cancer, since fat cells play a role in

estrogen synthesis.

" I think they're discovering that fat affects everything, " she said.