How Does Fat Kill Thee? Many Ways

Story location: http://www.wired.com/news/medtech/0,1286,63425,00.html

02:11 PM May. 11, 2004 PT

Research into the biology of fat is turning up some surprising new insights
about how obesity kills. The weight of the evidence: It's the toxic
mischief of the flesh itself.

Experts have realized for decades that large people die young, and the
explanation long seemed obvious. Carrying around all those extra pounds
must put a deadly strain on the heart and other organs.

Obvious but wrong, it turns out. While the physical burden contributes to
arthritis and sleep apnea, among other things, it is a minor hazard
compared with the complex and insidious damage wrought by the oily,
yellowish globs of fat that cover human bodies like never before.

A series of recent discoveries suggests that all fat-storage cells churn
out a stew of hormones and other chemical messengers that fine-tune the
body's energy balance. But when spewed in vast amounts by cells swollen to
capacity with fat, they assault many organs in ways that are bad for
health.

The exact details are still being worked out, but scientists say there is
no doubt this flux of biological cross talk hastens death from heart
disease, strokes, diabetes and cancer, diseases that are especially common
among the obese.

"When we look at fat tissue now, we see it's not just a passive depot of
fat," says Dr. Rudolph Leibel of Columbia University. "It's an active
manufacturer of signals to other parts of the body."

The first real inkling that fat is more than just inert blubber was the
discovery 10 years ago of the substance leptin. Scientists were amazed to
find that this static-looking flesh helps maintain itself by producing a
chemical that regulates appetite.

Roughly 25 different signaling compounds -- with names like resistin and
adiponectin -- are now known to be made by fat cells, Leibel estimates, and
many more undoubtedly will be found.

"There is an explosion of information about just what it is and what it
does," Dr. Allen Spiegel, director of the National Institute of Diabetes
and Digestive and Kidney Diseases, says of fat. "It is a tremendously
dynamic organ."

Fat tissue is now recognized to be the body's biggest endocrine organ, and
its sheer volume is impressive even in normal-size people. A trim woman is
typically 30 percent fat, a man 15 percent. That is enough fuel to keep
someone alive without eating for three months.

The fat cell's main job is to store our excess calories as fat. When people
grow obese, their fat cells swell with fat and can plump up to three times
normal size. As very overweight people get fatter still, they may also
layer on many more fat cells.

The problem is the volume of chemicals these oversize cells churn out, says
Dr. George Bray of Louisiana State University. "The big cell secretes more
of everything that it secreted when it was small. When you get more of
these things, they are not good for you."

Many scientists are trying to learn exactly what these excess secretions do
that is so harmful. The answers will help explain -- and perhaps offer
solutions to -- the real tragedy of the obesity epidemic, its disastrous
effect on health.

Obesity is a huge and growing killer, in the United States just slightly
behind smoking. Moderately obese people live two to five years less than
normal-size folks. For the severely obese, the reduction in life span may
be five to 10 years.

By far the biggest single threat of obesity is heart disease. Someone with
a body mass index over 30 has triple the usual risk. Scientists can
visualize many ways that fat cells' chemical flood contributes to heart
attacks, heart failure and cardiac arrest.

For instance, it has long been known that weight increases blood pressure.
Once doctors thought this was a matter of physics, the force needed to push
blood through the many more yards of blood vessels that nourish the extra
flesh.

But now it is clear that fat can trigger high blood pressure by making
blood vessels narrow in several chemical ways. For instance, it produces a
substance called angiotensinogen that is a powerful constrictor. At the
same time, it stimulates the sympathetic nerves to squeeze the circulatory
system. And that may just be the beginning.

"It's a very complicated system, and the more we learn about it, the more
complicated it becomes," says Dr. Xavier Pi-Sunyer, head of obesity
research at St. Luke's Roosevelt Hospital Center in New York City.

One of the clearest hazards of overfilled fat cells is their influence on
the body's production and use of insulin, the hormone that instructs the
muscle to burn energy and the fat cells to store it. Oversize fat cells
blunt the insulin message, in part by leaking fat into the bloodstream. So
the pancreas must compensate by making more insulin and other proteins.

Scientists now understand that increasing insulin levels -- part of a
condition called insulin resistance -- are particularly harmful. They can
directly damage the walls of arteries and lead to clogging.

That leaking fat may also infiltrate the heart muscle, contributing to
congestive heart failure. Misplaced deposits of fat can also ruin the liver
and have become the second-leading reason for liver transplants after
hepatitis B.

Fat cells churn out a variety of proteins that cause inflammation, too.
These may be especially destructive to the gunky buildups in the arteries,
causing them to burst and triggering heart attacks and strokes.

These inflammatory proteins and other fat-driven chemicals, such as growth
hormones, may also contribute to one of the less-appreciated consequences
of obesity -- cancer.

"There is now conclusive evidence that obesity causes some cancers and
strong evidence that it contributes to a wide variety of others," says Dr.
Michael Thun, epidemiology chief at the American Cancer Society.

The cancer society estimates that staying trim could eliminate 90,000 U.S.
cancer deaths a year. Among the varieties most clearly linked to weight are
cancer of the breast, uterus, colon, kidney, esophagus, pancreas and
gallbladder.

The best evidence of how obesity causes malignancy is in breast cancer in
older women. When the ovaries shut down after menopause, fat tissue becomes
the primary producer of estrogen, which in turn can fuel the growth of
breast tumors.

The heavier women are when diagnosed with breast cancer, the more likely
they are to die from the disease, says Dr. Michelle Holmes of Boston's
Brigham and Women's Hospital. "Presumably it's because their cancers are
dependent on estrogen, and heavier women have more estrogen."

Still, big-ticket killers like heart disease and cancer only start the long
list of obesity's health ills. Among other things, obese people are more
prone to depression, gallstones, even dying when in car accidents.

Says Dr. Michael Jensen of the Mayo Clinic, "There are so many ways that
obesity can kill you."

Fat tissue is now recognized to be the body's biggest endocrine organ, and
its sheer volume is impressive even in normal-size people. A trim woman is
typically 30 percent fat, a man 15 percent. That is enough fuel to keep
someone alive without eating for three months.

If ANY of this is true (and I am thoroughly skeptical about that), then
please explain to me why an obese person of about 1200 pounds began to
starve himself and died of starvation (or was it malnutrition?) at about 600
pounds.

Personally I think the concept that fat cells are endocrine glans is
incorrect and misleading.

Em

Auntie Em wrote:
Fat tissue is now recognized to be the body's biggest endocrine organ, and
its sheer volume is impressive even in normal-size people. A trim woman is
typically 30 percent fat, a man 15 percent. That is enough fuel to keep
someone alive without eating for three months.


If ANY of this is true (and I am thoroughly skeptical about that), then
please explain to me why an obese person of about 1200 pounds began to
starve himself and died of starvation (or was it malnutrition?) at about 600
pounds.

Because the conversion from fat to energy is very expensive, and you
need some carbs to make it happen. So it's not a good idea to rely only
on your fat to feed you, although it can get you going without eating
for a long time. I figure everyone can go at least two weeks without
eating at all, after that it depends on your body. This kind of "diet"
will leave you very tired and you won't have energy for pretty much anyting.


--
polar bear

"Auntie Em" Auntie wrote in message
...
Fat tissue is now recognized to be the body's biggest endocrine organ,
and
its sheer volume is impressive even in normal-size people. A trim woman
is
typically 30 percent fat, a man 15 percent. That is enough fuel to keep
someone alive without eating for three months.

If ANY of this is true (and I am thoroughly skeptical about that), then
please explain to me why an obese person of about 1200 pounds began to
starve himself and died of starvation (or was it malnutrition?) at about
600
pounds.

Well it's all relative. If you are 1200 pounds and eat only 1500 calories,
it is very possible to starve yourself to death. This is because your body
cannot process fat from your body at a high enough rate to meet the body's
demand for energy and you will die from the lack of energy. To sustain a
living physical mass of 1200 pounds (assuming very little of it was water &
other non-living tissue), one would need an energy consumption of about
10,000 calories or more. However, if you are only 100 pounds and eat 2000
calories, it is very possible (depending on numerous factors) that you will
*gain* weight.

This is why the very overweight should GRADUALLY decrease energy
consumption, rather than going on a strict low cal diet. Low cal is very
relative, and what is low cal for one person might be STARVATION for another
(and likewise what is low cal for one might be near maintenence for
another). This is why the very overweight tend to fail at diets. They make
the mistake of starving themselves (with weight watchers, jenny craig,
liquid fasts, etc) instead of slowly cutting back on food. The starvation
depletes leptin which triggers physiological starvation adaption. Leptin
depletion leads to food obsession, insatiable appetite, binge eating, and
temporarily slowed metabolism - all of which lead to diet failure and weight
gain.

Personally I think the concept that fat cells are endocrine glans is
incorrect and misleading.

Em


There's nothing misleading about it. Fat cells are a living, breathing,
energy processing metabolically active tissue. Because of this, fat cells
are an effect of as well as affected by the endocrine system. An
overabundance of fat tends to imply endocrinological system is not in good
function - hypothyroidism, Cushing's syndrome, as well as the spectrum of
insulin resistance disorders (hypoglycemia/diabetes/PCOS, etc.) all occur
with much greater frequency among the overweight (and the etiology of these
diseases also is conducive to fat storage).

"Auntie Em" Auntie wrote in message

Fat tissue is now recognized to be the body's biggest endocrine
organ, and its sheer volume is impressive even in normal-size
people. A trim woman is typically 30 percent fat, a man 15 percent.
That is enough fuel to keep someone alive without eating for three
months.

If ANY of this is true (and I am thoroughly skeptical about that),
then please explain to me why an obese person of about 1200 pounds
began to starve himself and died of starvation (or was it
malnutrition?) at about 600 pounds.
snip

Total starvation results in death within 8 to 12 weeks. You can argue that
12 weeks equals 3 months but to me "keeping someone alive" doesn't mean
ready to expire at any second.
http://www.merck.com/mrkshared/mmanu...hapter2/2b.jsp

The reason fat people die of starvation while they're still fat is because
it takes carbohydrates to perform many metobolic functions. The body can and
does manufacture the carbohydrates it needs by converting protein to
glucose. However, when someone is starving themselves and not providing
protein from outside sources the body will canabalize its own muscles to get
the protein it needs for the conversion. The heart is a muscle.
--
Jeri
"Change is inevitable, except from vending machines."

"Jeri" wrote in message
news
The reason fat people die of starvation while they're still fat is because
it takes carbohydrates to perform many metobolic functions. The body can
and
does manufacture the carbohydrates it needs by converting protein to
glucose. However, when someone is starving themselves and not providing
protein from outside sources the body will canabalize its own muscles to
get
the protein it needs for the conversion. The heart is a muscle.

That's right. I had an uncle who went on some sort of "soup diet" when he
was in his mid sixties. He'd been obese all his life (or all mine, anyway),
and lost a lot of weight. And then died of heart failure.

At least he was a trim corpse. But I don't think it was worth it.