It's
how we're wired
Howard Hughes Medical Institute, Science Daily
If you're finding it difficult to stick to a weight-loss diet, scientists at the Howard Hughes Medical Institute's Janelia Research Campus say you can likely blame hunger-sensitive cells in your brain known as AGRP neurons.
According to new experiments, these neurons are responsible for the unpleasant feelings of hunger that make snacking irresistible.
The
negative emotions associated with hunger can make it hard to maintain a diet
and lose weight, and these neurons help explain that struggle, says Scott
Sternson, a group leader at Janelia.
In an environment where food is readily
available, their difficult-to-ignore signal may seem like an annoyance, but
from an evolutionary point of view, they make sense.
For earlier humans or animals in the wild, pursuing food or water can mean venturing into a risky environment, which might require some encouragement.
For earlier humans or animals in the wild, pursuing food or water can mean venturing into a risky environment, which might require some encouragement.
"We suspect that what
these neurons are doing is imposing a cost on not dealing with your physiological
needs," he adds.
AGRP
neurons do not directly drive an animal to eat, but rather teach an animal to
respond to sensory cues that signal the presence of food. "We suspect that
these neurons are a very old motivational system to force an animal to satisfy
its physiological needs. Part of the motivation for seeking food is to shut
these neurons off," says Sternson, whose team also demonstrated that a
different set of neurons is specialized to generate unpleasant feelings of
thirst.
Sternson and his colleagues published their findings in the journal Nature on
April 27, 2015.
Hunger
affects nearly every cell in the body, and several types of neurons are
dedicated to making sure an animal eats when energy stores are low. But
Sternson says that until now, what scientists had learned about those neurons
had not completely matched up to something we already know: hunger is
unpleasant.
"There
was an early prediction that there would be neurons that make you feel bad when
you were hungry or thirsty. This made sense from an intuitive point of view,
but all of the neurons that had been looked at seemed to have the opposite
effect," he says.
In earlier studies, researchers found that neurons that
promoted eating did so by increasing positive feelings associated with food. In
other words -- not surprisingly -- hunger makes food tastes better.
Some
scientists had begun to suspect their ideas about a negative signal in the
brain motivating hunger might be wrong. But their knowledge of the system was
incomplete. AGRP neurons, located in a regulatory area of the brain known as
the hypothalamus, were clearly involved in feeding behaviors:
When the body
lacks energy, AGRP neurons become active, and when AGRP neurons are active,
animals eat. But no one had yet investigated those cells' strategy for
generating that motivation.
Postdoctoral
researcher Nicholas Betley and graduate student Zhen Fang Huang Cao began to
address the question with a series of behavioral experiments. In the first,
they offered well-fed mice two flavored gels -- one strawberry and the other
orange.
Neither gel contained any nutrients, but the hungry mice sampled them
both. Then the scientists' manipulated the hunger signals in the animals'
brains by switching AGRP neurons on while they consumed one of the two flavors.
In subsequent tests, the animals avoided the flavor associated with the false
hunger signal.
In
a reverse experiment, the scientists switched AGRP neurons off while hungry
animals consumed a particular flavor. The animals developed a preference for
the flavor choice that led to silencing of AGRP neurons, suggesting they were
motivated to turn off the cells' unpleasant signal.
In further experiments, the
scientists found that mice also learn to seek out places in their environment
where AGRP neurons had been silenced and avoid places where those cells were
active.
Next,
postdoctoral researcher Shengjin Xu used a tiny, mobile microscope to peer
inside the brains of hungry mice and monitor the activity of AGRP neurons. As
expected, the cells were active until the mice found food.
What was surprising,
Sternson says, is that mice did not actually have to eat to quiet the neurons.
Instead, the cells ceased activity as soon as an animal saw food -- or even a
signal that predicted food. And their activity remained low while the animal
was eating.
That
wouldn't make sense if the job of AGRP neurons was to make food taste better or
if they directly controlled the individual actions that go into eating, which
were two possibilities, Sternson says. But to encourage eating, a negative
signal would need to turn off when an animal consumed food. So their imaging
experiments further supported what they had learned in their previous
experiments.
The
team later conducted similar experiments in which they manipulated
thirst-sensitive neurons instead of AGRP neurons.
Those neurons, found in a
part of the brain known as the subfornical organ (SFO) behaved similarly:
animals avoided places where the SFO neurons had been active, indicating that
the cells generated a negative feeling.
Again, the findings were consistent with
everyday experience: "There's a similar motivational quality to hunger and
thirst," Sternson says. "You want them to end."
But although
AGRP and SFO neurons motivate similar behaviors, their goals are very specific:
AGRP neurons only drive animals to eat and SFO neurons only drive animals to
drink. Recent independent work by HHMI researcher Charles Zuker at Columbia
University has also shown that a circuit in the SFO regulates thirst.
In
further experiments, Sternson's team will investigate similarities and
differences between the two groups of cells. In addition, his group is
interested in understanding more about how to interfere with the functions of
AGRP neurons, which, in the future, might make it easier to keep those extra
pounds off next time you go on a diet.
Video: https://vimeo.com/57082414
Story Source:
The
above story is based on materials provided
by Howard Hughes
Medical Institute. Note: Materials
may be edited for content and length.
Journal Reference:
J. Nicholas Betley, Shengjin Xu, Zhen Fang Huang Cao, Rong Gong,
Christopher J. Magnus, Yang Yu, Scott M. Sternson. Neurons for hunger and thirst transmit a
negative-valence teaching signal. Nature, 2015;
DOI:10.1038/nature14416
Cite This Page:
Howard Hughes Medical Institute. "Hate to diet? It's how
we're wired." Science Daily,
27 April 2015. <www.sciencedaily.com/releases/2015/04/150427124633.htm>.
