Ghrelin enhances brain's reward machinery
Kofi
Why Some Continue to Eat When Full: Researchers Find Clues
ScienceDaily (Dec. 28, 2009) � The premise that hunger makes food look
more appealing is a widely held belief -- just ask those who cruise
grocery store aisles on an empty stomach, only to go home with a full
basket and an empty wallet.
Prior research studies have suggested that the so-called hunger hormone
ghrelin, which the body produces when it's hungry, might act on the
brain to trigger this behavior. New research in mice by UT Southwestern
Medical Center scientists suggest that ghrelin might also work in the
brain to make some people keep eating "pleasurable" foods when they're
already full.
"What we show is that there may be situations where we are driven to
seek out and eat very rewarding foods, even if we're full, for no other
reason than our brain tells us to," said Dr. Jeffrey Zigman, assistant
professor of internal medicine and psychiatry at UT Southwestern and
co-senior author of the study appearing online and in a future edition
of Biological Psychiatry.
Scientists previously have linked increased levels of ghrelin to
intensifying the rewarding or pleasurable feelings one gets from cocaine
or alcohol. Dr. Zigman said his team speculated that ghrelin might also
increase specific rewarding aspects of eating.
Rewards, he said, generally can be defined as things that make us feel
better.
"They give us sensory pleasure, and they motivate us to work to obtain
them," he said. "They also help us reorganize our memory so that we
remember how to get them."
Dr. Mario Perello, postdoctoral researcher in internal medicine and lead
author of the current study, said the idea was to determine "why someone
who is stuffed from lunch still eats -- and wants to eat -- that
high-calorie dessert."
For this study, the researchers conducted two standard behavioral tests.
In the first, they evaluated whether mice that were fully sated
preferred a room where they had previously found high-fat food over one
that had only offered regular bland chow. They found that when mice in
this situation were administered ghrelin, they strongly preferred the
room that had been paired with the high-fat diet. Mice without ghrelin
showed no preference.
"We think the ghrelin prompted the mice to pursue the high-fat chow
because they remembered how much they enjoyed it," Dr. Perello said. "It
didn't matter that the room was now empty; they still associated it with
something pleasurable."
The researchers also found that blocking the action of ghrelin, which is
normally secreted into the bloodstream upon fasting or caloric
restriction, prevented the mice from spending as much time in the room
they associated with the high-fat food.
For the second test, the team observed how long mice would continue to
poke their noses into a hole in order to receive a pellet of high-fat
food. "The animals that didn't receive ghrelin gave up much sooner than
the ones that did receive ghrelin," Dr. Zigman said.
Humans and mice share the same type of brain-cell connections and
hormones, as well as similar architectures in the so-called "pleasure
centers" of the brain. In addition, the behavior of the mice in this
study is consistent with pleasure- or reward-seeking behavior seen in
other animal studies of addiction, Dr. Zigman said.
The next step, Dr. Perello said, is to determine which neural circuits
in the brain regulate ghrelin's actions.
Other UT Southwestern researchers involved in the study were Dr. Ichiro
Sakata, postdoctoral researcher in internal medicine; Dr. Shari
Birnbaum, assistant professor of psychiatry; Dr. Jen-Chieh Chuang,
postdoctoral researcher in internal medicine; Sherri Osborne-Lawrence,
senior research scientist; Sherry Rovinsky, research assistant in
internal medicine; Jakub Woloszyn, medical student; Dr. Masashi
Yanagisawa, professor of molecular genetics and a Howard Hughes Medical
Institute investigator; and Dr. Michael Lutter, co- senior author and
assistant professor of psychiatry.
The work was supported by the National Institutes of Health, the
Foundation for Prader-Willi Research, and the National Alliance for
Research on Schizophrenia and Depression.
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Story Source:
Adapted from materials provided by UT Southwestern Medical Center, via
EurekAlert!, a service of AAAS.
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Journal Reference:
1. Mario Perello, Ichiro Sakata, Shari Birnbaum, Jen-Chieh Chuang,
Sherri Osborne-Lawrence, Sherry A. Rovinsky, Jakub Woloszyn, Masashi
Yanagisawa, Michael Lutter, Jeffrey M. Zigman. Ghrelin Increases the
Rewarding Value of High-Fat Diet in an Orexin-Dependent Manner.
Biological Psychiatry, 2009; DOI: 10.1016/j.biopsych.2009.10.030