Cell: Compulsive overeating and sugar addiction are major threats to human
health, but potential treatments face the risk of impairing normal
feeding behaviors that are crucial for survival. A study published
January 29th in the journal Cell reveals a reward-related
neural circuit that specifically controls compulsive sugar consumption
in mice without preventing feeding necessary for survival, providing a
novel target for the safe and effective treatment of compulsive
overeating in humans.
"Although obesity and Type 2 diabetes are major problems in our
society, many treatments do not tackle the primary cause: unhealthy
eating habits," says senior study author Kay Tye of the Massachusetts
Institute of Technology. "Our findings are exciting because they raise
the possibility that we could develop a treatment that selectively curbs
compulsive overeating without altering healthy eating behavior."
Compulsive overeating is a type of reward-seeking behavior, similar
to drug addiction. But the major difference between the two behaviors is
that eating is required for survival, underscoring the need to tease
apart brain circuits involved in compulsive overeating versus normal
feeding to develop safe and effective therapies. Tye and her team
suspected that a neural pathway from the lateral hypothalamus to the
ventral tegmental area might play an important role in compulsive
overeating because these brain regions have been implicated in
reward-related behaviors such as eating, sexual activity, and drug
addiction.
To test this idea, Tye and her team used a technique called
optogenetics, which involves genetically modifying specific populations
of neurons to express light-sensitive proteins that control neural
excitability, and then delivering either blue or yellow light through an
optic fiber to activate or inhibit those cells, respectively.
Activation of the pathway from the lateral hypothalamus to the ventral
tegmental area caused well-fed mice to spend more time feeding and
increased the number of times mice poked their nose into a port to
receive a sugar reward, even when they had to cross a platform that
delivered foot shocks to get to the reward. By contrast, inhibition of
the same pathway reduced this compulsive sugar-seeking behavior without
decreasing food consumption in hungry mice, suggesting that different
neural circuits control feeding in hungry animals.
In an independent study also published January 29th in Cell,
Garret Stuber of the University of North Carolina School of Medicine
and his team similarly used an optogenetic approach in mice to identify
neurons in the lateral hypothalamus that control both feeding and
reward-seeking behavior. By imaging the activity of hundreds of
individual lateral hypothalamus neurons as the mice freely explored an
area with food or worked to obtain a sweet reward, they further
uncovered distinct subsets of neurons that either mediate food-seeking
behavior or respond to reward consumption.
According to Tye, it makes sense that brain circuits evolved to
support binging on scarce, sugary foods whenever these valuable sources
of energy become transiently available during certain seasons. But in
the winter, it might be adaptive for separate neural circuits to drive
hungry animals to eat whatever type of food is available but to consume
less overall to ration out limited resources.
"However, in our modern day society, there is no scarcity of
palatable foods, and high-sugar or high-fat foods are often even more
available than fresh produce or proteins," Tye says. "We have not yet
adapted to a world where there is an overabundance of sugar, so these
circuits that drive us to stuff ourselves with sweets are now serving to
create a new health problem. The discovery of a specific neural circuit
underlying compulsive sugar consumption could pave the way for the
development of targeted drug therapies to effectively treat this
widespread problem."