It’s amazing that we’re not
more obese than we are.
—RANDY SEELEY, PHD
Leptin was keeping the mice skinny, suppressing or
regulating their appetite. High levels of leptin, it was
thought, tell the brain “enough,” producing a sated
feeling. Low levels, on the other hand, were connected to
feelings of hunger.
Think of the hormone as a radio signal that’s emitted
by the fat cells and picked up by the brain. The message?
You’ve got enough energy stored in the form of fat.
Fully loaded fat cells equal a strong leptin signal. When
the brain stops receiving the leptin transmissions, it
concludes that fat stores are low—and pushes the body
to replenish them by making you feel hungry.
Randy Seeley, PhD, is a University of Michigan
calories larger than they were two decades ago. Yet the
scientist who’s been studying hormones and obesity
for decades. To Seeley, one of the most remarkable
things about this elaborate signaling system is how
well it works. Like a plane on autopilot, the body takes
in different variables, from how much we’re exercising
to the calorie content of the food we’re eating. Then, by
making us feel more or less hungry, or speeding up or
slowing down our metabolism, the hormones interact
with the brain to make tiny course corrections to keep
us within the right weight range. “It’s a combination of
all these signals that allows you to be that accurate,”
Seeley says. “It’s amazing that we’re not more obese than
Consider this: Typical restaurant meals are 200
average weight gain among American adults is only a
pound each year—the equivalent of 4,000 extra calories.
That means that over the course of a year, the average
American adult consumes only 11 excess calories a day.
In other words, we’re kept almost exactly on target by
an extraordinarily complex system of hormones and
Seeley says the system of hunger hormones may
even be causing us to leave food on our plates as portion
sizes grow. Meanwhile, our metabolism compensates
and burns more energy. Though Americans are 15
pounds heavier on average than they were 20 years
ago, given the increase in portion sizes and time spent
sitting down, we could be far heavier, Seeley argues.
ormones are molecules that allow the body
to communicate with itself. You may be
most familiar with insulin, which signals
muscle cells to absorb glucose from the
bloodstream. Other hormones control or
in;uence everything from sleep and sex to mood,
movement, and growth.
Several hormones, it turns out, also play a big
role in hunger and its opposite: satiety, the feeling of
fullness. Over the past two decades, researchers have
learned a lot about how hunger hormones work, and
along the way they’ve discovered that there’s much
more we don’t yet understand.
SURVIVAL OF THE FITTEST
The urge to eat is motivated by a feeling of
hunger, which is in;uenced by factors such as a
food’s savory appeal, the body’s fat stores, and
its perceived need for energy. “As you get more
energy deprived, you get more hungry,” says
Zachary Knight, PhD, a researcher at the University
of California–San Francisco School of Medicine.
Satiety—the “I’ve eaten enough” feeling—is also the result
of hormones signaling to the brain.
All of these impulses have deep evolutionary roots.
Just as it’s important for the body and brain to work
together to make sure you eat, systems have also evolved
to make sure you don’t eat too much. Feeding was just
one behavior that kept our distant ancestors alive,
similar to hiding from predators, migrating, or mating—
fat is important for fertility and surviving famines, after
all. But at the same time, someone who spent too much
time eating wouldn’t survive. The regulatory system we
evolved so long ago still manages our eating impulses
today. “The [person] constantly has to be weighing what
is most important for survival,” says Knight. “You want
the system to be sensitive to your real need so you can
evaluate what you need to be doing.”
For decades, scientists have been researching the role of
two hormones in regulating hunger, food preferences, and
satiety. Called leptin and ghrelin, the two compounds act
as signals from the body to the brain and seem to regulate
appetite and satiety.
The discovery of leptin’s role in weight gain was based
on a simple experiment in mice with a mutation that
“knocked out” the gene that tells fat cells to produce
leptin, leaving the rodents incapable of making leptin by
themselves. When leptin-free mice were injected with
the hormone, they kept their weight stable and healthy.
But leptin-free mice who weren’t given the hormone ate
too much and became obese. The natural conclusion: