nwanted, unloved, yet often over-
abundant, few have much regard for
fat. Scientists, too, long thought of fat
cells as good-for-nothing layabouts
unworthy of attention; containers stuffed with
energy to be released at the body’s command.
So stuffed, in fact, that many other parts of the
cell were thought too squeezed to function.
So when, in the early 1990s, graduate stu-
dent Gökhan Hotamisligil at Harvard Medi-
cal School in Boston caught fat tissue doing
something biologically remarkable, at first
he did not believe his own data. He repeated
the work many times, but it always came out
the same: fat from obese mice was produc-
ing TNFα — the hot inflammatory molecule
of the day because of its role in autoimmune
disorders such as arthritis. After he and his
colleagues published their observation in
, others in the field remaned sceptical.
Hotamisligil says he was invited to speak at
meetings “for entertainment purposes”.
Since then, fat cells have had an image
change. This started with the 1995 discovery
that fat secretes leptin, a hormone that tells the
brain “I’m full, stop eating”. In retrospect, it
makes sense that fat should tell the body how
much energy it is storing and how much more
to take in. But when it came to obesity-related
problems such as type 2 diabetes and cardio-
vascular disease, fat was still not seen as an
active player. These conditions were thought
to be caused by an excess of nutrients from
overeating, or a glut of fatty molecules spilling
out of storage into the bloodstream.
More than a decade on, fat has a higher sta-
tus. Scientists know that fat cells pump out ten
or more molecules called adipokines that carry
messages to the rest of the body. And ‘fat’ fat
cells — those common in the obese and which
are themselves bloated with lipids — send differ-
ent molecular messages from ‘thin’ fat cells.
The signals from ‘fat’ fat are thought to
directly promote insulin resistance and to
trigger inflammation, which may, in turn,
cause type 2 diabetes, cardiovascular dis-
ease, increased cancer risk and other obesity-
associated problems. This means that it might
be possible to treat these conditions without
shedding the fat itself. Some remedies might
be as simple as using anti-inflammatory drugs
that have been around for more than a century;
others might involve persuading obese fat cells
to behave like skinny ones.
Society may still view fat with resignation
or even revulsion, but biologists have moved
on. “No one appreciated the higher functions
of fat,” says Barbara Kahn, a diabetes and
obesity researcher at Harvard’s Beth Israel
Deaconess Medical Center in Boston. “The fat
THE TWO FACES OF FAT
No longer viewed as inert packets of energy, fat cells are two-faced masterminds of metabolism.