Discoveries Show How Obesity Kills
Mon May 10, 2:16 PM
By DANIEL Q. HANEY, AP Medical Editor
- 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 to 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 crosstalk 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 liver 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."
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EDITOR'S NOTE: Medical Editor Daniel Q. Haney is a
special correspondent for The Associated Press.
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On the Net:
obesityresearch.nih.govobesityresearch.nih.govOpen ↗
Copyright 2004 The Associated Press.