PITY the world’s most hated tissue. We spend millions trying to starve or
carve it out of our bodies. Relentlessly persecuted, body fat is caricatured as
a lard-guzzling monster that just sits on your hips and belly, passively
absorbing the calories you eat. But body fat is emerging as more complex and
important than we ever imagined. “Fat is an organ,” says Simon Coppack, an
obesity researcher at the Royal London Medical School. “You should probably
think of it as a little bit like the liver.”
In some ways, our body fat, or adipose tissue, is nothing like our other
organs. For one thing, it’s spread throughout the body in a number of
specialised depots. You’ll find them under your skin (subcutaneous fat), packed
around internal organs, especially your guts and kidneys, lining your belly, and
encasing your lymph nodes. But fat is turning out to be the body’s wise manager,
and like all good managers, it delegates specific tasks to different
departments.
Take a closer look at adipose tissue and you will see that it is made up of a
honeycomb of enormous spherical cells, called adipocytes, each filled to the
brim with a droplet of fat. Fat is a fairly good insulator and might help to
keep us warm, although some researchers argue that in humans it is not
specifically adapted for this purpose. And thanks to its honeycomb structure,
adipose tissue is the ultimate biological Bubble Wrap—cushioning your
joints and heels, and padding out your fingertips and eye sockets. While these
“mechanical” adipose depots are pretty quiet on the metabolic front, others play
a far more active role. Served with a network of blood vessels and wired into
the nervous system, fat is poised to respond to your body’s every energy
need.
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People born with a rare condition called Berardinelli-Seip syndrome give some
clues to just how vital fat is. These people have almost no body fat—only
a few bits of padding. With no fat cells to fill, any fat eaten ends up in the
liver and muscles, damaging the liver, and causing insulin resistance and so
diabetes. Children with the condition are gaunt and voraciously hungry. Later in
life, they suffer problems with their reproductive systems, and are likely to
die young.
Although most of us know that having a bit of fat will tide us over in times
of starvation, few appreciate its vital and dynamic role as a store for
smoothing out the highs and lows in our daily food intake. Without it we’d be
permanently famished, eating almost constantly just to stay alive. Although the
body can store energy in the liver and muscles in the form of glycogen—a
polymer made by stringing lots of glucose molecules together—these stores
are limited, and nowhere near as efficient as fat. “It isn’t just for rainy
days, it’s basic housekeeping,” says Coppack.
“The amount of fat that goes in and out of adipose tissue in a typical day is
actually enormous,” says Keith Frayn, a metabolism expert at the University of
Oxford. “It’s best regarded as a sort of buffer.” Following a meal, the liver,
muscles and adipose tissue decide between them how to divvy up the nutritional
booty. In response to rising levels of insulin, your liver and muscles snap up
carbohydrates, while adipocytes gorge themselves on the fat droplets in the
blood, storing it in a liquid form called triacylglycerol. When insulin levels
fall, or if your body kick-starts its stress response when you’re fighting an
infection or exercising, for example, enzymes in your adipocytes carve up
triacylglycerol, releasing fuel back into the circulation.
All this expertise is very impressive, but why are scientists now calling
body fat an organ? The answer lies in the discovery that it sits at the heart of
a complex and wide-ranging communications network. “It made fat much cleverer
than it was thought to be before,” says Steve O’Rahilly, an adipose tissue
expert from the University of Cambridge.
The organ concept really took off when researchers found that it makes a
hormone called leptin that briefs the brain on the state of the body’s energy
coffers. This put an end to the concept of adipose tissue as passive: “Leptin is
so fascinating, because this is a significant new hormone system of major
importance in humans,” says Frayn. The level of leptin circulating in the blood
is monitored by a brain region called the hypothalamus, and is related to the
amount of fat we have stashed away. The hypothalamus is the nerve centre of our
primitive motivations, managing vital processes such as food intake, weight,
sleep, body temperature and reproduction.
In healthy people, leptin is involved in a delicate balancing
act—putting a brake on eating if we have too much fat, and ringing alarm
bells if our energy accounts start wandering into overdraft. This means that
although your weight might fluctuate from week to week, in the longer term it
tends to remain stable. A lot of research has focused on how leptin damps down
appetite, in the hope of developing anti-fat drugs. But some researchers think
that it is more important at the other extreme—to stop us from starving to
death. Once leptin drops off the bottom of the scale, the starvation response
kicks in—triggering a voracious appetite and a wash of stress hormones as
the body turns all its attention to restocking its precious reserves.
Although such a response would be essential for survival in an environment
with an erratic food supply, it’s redundant if you’re living next door to a
Chinese takeaway. But there’s more to leptin than meets the eye—it also
helps the body to decide whether it has enough resources to afford the expensive
luxuries of reproduction and adolescence.
The voluptuous Venusian fertility goddesses worshipped by our ancestors are a
far cry from the scrawny superwaifs paraded on catwalks—and with good
reason. Women with very little body fat—anorexics and super-skinny
ballerinas—don’t have periods. This makes perfect sense. Nourishing a
developing fetus is a huge drain on a woman’s energy stores. “If you went into a
pregnancy malnourished, that would be catastrophic for both the baby and the
mother,” says Coppack. “It’s crucial that the mother’s system knows that she has
enough energy on board.”
A feminine issue?
Women generally have more fat than men, some 20 to 25 per cent of their body
weight, while male bodies are generally about 15 to 20 per cent fat. Women need
a slow and steady supply to support pregnancy and lactation—a role
fulfilled by subcutaneous fat, says O’Rahilly. Men depend more on belly fat,
which perhaps once sustained the more immediate needs of a hunting ancestor. To
this day, belly fat is used and replaced three times faster than subcutaneous
fat. So if all else fails, blame the paunch on the Pleistocene.
Girls born with leptin deficiency are not only infertile—they never go
through adolescence in the first place. O’Rahilly has been treating a
leptin-deficient girl with the hormone and she has now entered normal
adolescence. But fat isn’t just a feminine tissue. Boys need leptin too—to
tell their bodies that they have enough energy stores to see them through the
energetically expensive process of puberty—such as the adolescent growth
spurt. Although it’s extremely rare, men with no leptin are Peter
Pans—they will never reach sexual maturity.
Fat is also important at the end of a woman’s reproductive life. Adipose
tissue helps convert the precursors for sex hormones into their active forms,
and is an important source of them for protecting the bones of women after the
menopause. But this protection is a double-edged sword—excess amounts of
body fat can predispose women to hormone-sensitive cancers such as breast and
gall-bladder cancer. Men who have excessive amounts of body fat can find
themselves becoming slightly feminised, losing facial hair, for example, as well
as having an increased cancer risk.
And while fat is busy monitoring whether we’re in good shape, it also picks
up when we’re under the weather—a sort of crisis management system. Leptin
belongs to a family of molecules called cytokines—hormonal signals
broadcast by white blood cells to regulate the immune response. If you’re under
attack by a flu virus, say, cytokines flood your body, helping to raise the
alarm. They also temporarily suppress your appetite and make you feel tired and
woolly headed as they channel the body’s resources into quashing the viral
invasion.
Leptin’s role in the immune system comes into its own in times of
starvation. As a starving person’s energy economy plummets deeper into
recession, their adipose tissue is forced to save its reserves for vital
functions—by slashing the defence budget. About 15 per cent of your energy
budget goes on your immune system, so it’s a logical place to make cuts if
you’re forced to run your metabolism on a shoestring.
Fat does this by withdrawing leptin’s crucial support for the linchpin of our
defences, helper T cells. These cells coordinate our vastly complex immune
response—which is why losing them through HIV infection is so disastrous.
All T cells come with a receptor for leptin, and depend on the hormone for
permission to carry out their duties. Once the amount of fat, and hence leptin
in the circulation, dips below a critical level, T cells have to sit tight and
await further orders. “All the effects of leptin take place at the lower end of
the scale,” says Bloom. Once you’ve got some fat, everything behaves normally,
but if you’ve got none, it switches off.
But far from barking orders to the troops from a remote command bunker, fat
could also be actively patrolling our front line defences. Adipose tissue makes
a number of cytokines, and is also a major source of a set of proteins called
“complement”. Complement proteins are the immune system’s precision bombs. When
released, they punch holes in the walls of invading bacteria or diseased cells
that antibodies have marked out for destruction. Although fat’s role in this
form of immunity is poorly understood and not yet proven, adipose tissue lines
our outer and inner body surfaces, such as under the skin and around the gut,
and is ideally placed to confront these unwanted interlopers, says O’Rahilly.
This may be particularly important in protecting us from intestinal infection,
he adds—after all, your guts are a crawling cosmopolitan metropolis of
bacteria.
Creeping fat
He suggests that it could help explain a bizarre phenomenon called “creeping
fat”. For example, if you suffer a perforated intestine, the omentum, a fibrous
sheet of tissue lying over the gut where the belly fat is stored, sticks to the
perforation and seals it off, rather like a bicycle puncture repair kit.
Fat may have other supporting roles for local immune responses too. Caroline
Pond, a biologist at the Open University in Milton Keynes, is a pioneer in
adipose tissue research (Â鶹´«Ă˝, 22 April 1995, p 34), and has
made some intriguing discoveries about the thin shells of adipose tissue that
surround our lymph nodes. These nodes are like garrisons, harbouring white blood
cells and staking out the body’s vulnerable spots, ready to collar any microbial
trespassers.
Pond and her colleagues have found that adipocytes that surround the major
lymph nodes are uniquely responsive to the signals sent out by white blood cells
when they encounter a microbial invasion. The adipocytes respond by provisioning
the troops with the essential, tailor-made supplies that they need to see off
the bad guys. “It’s a bit like having a first-aid box that’s always there,” says
Pond. Lymph nodes can deal with local skirmishes without having to raise a
global red-alert and compete with other tissues for blood-borne fuel.
So fat is a truly multi-talented organ. A jack of all trades, it does
everything from balancing your energy books and regulating your fertility, to
supplying and commanding your defences. Some scientists think it may even have a
say in our mood, behaviour or hormonal responses. “There’s just a whole growing
body of evidence that leptin elicits a range of novel physiological effects,”
says Jeffrey Friedman, a professor at Rockefeller University, New York, who led
the team that first discovered leptin. “There are leptin receptors throughout
the brain—there are lots of them everywhere,” says Bloom. Exactly what
they’re up to is anybody’s guess.
Perhaps, like the lymph nodes, other organs have their own special supply of
fat too. The heart, a constantly working muscle, is surrounded by adipose
tissue—so does it have it’s own personalised fuel supply? “It’s a very
attractive idea,” says Frayn, “but there is no anatomical evidence for
łŮłó˛ąłŮ.”
We may be just beginning to unearth the secrets of this underrated and
much-maligned tissue. But the picture that is emerging is one of a highly
complex and delicately balanced system. Much of the bad press that body fat gets
is perfectly justified—obese people are far more susceptible to heart
disease and diabetes, for example. But the wholesale vilification of this
versatile organ is unfair. Will we ever learn to love our adipocytes? Fat
chance. But maybe we will learn to appreciate their services and realise that
fat isn’t all bad. Fat is beautiful.
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Further reading:
Adipose tissue as an endocrine and paracrine organ by V. Mohamed-Ali, J. H. Pinkney and Simon Coppack
International Journal of Obesity and Related Metabolic Disorders, vol 22, p 1145 (1998) -
The Fats of Life by Caroline M. Pond,
Cambridge University Press (1998) -
Leptin latest can be found on Â鶹´«Ă˝â€™s conference report
website, from the 18th International Congress of Biochemistry and Molecular
Biology at www.newscientist.com/conferences