Sugar is processed differently in the brains of obesity-prone vs. obesity-resistant rats
Molecular insights point to neuronal underpinnings of obesity

Date:
February 2, 2023
Source:
Michigan Medicine - University of Michigan
Summary:
A new study tracked what happens in the brains of rats in real
time in the brain when presented with glucose, a type of sugar,
labeled with a tracer. The tracer allowed the researchers to
measure this new sugar in the brain.


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FULL STORY ==========================================================================
On a diet? Perhaps you're avoiding sweets or carbs altogether or curbing
late- night munchies. These are examples of behavior modifications and
when it comes to food, avoiding those diet triggers can be pretty hard
to do.


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To understand what drives people to overeat, scientists are looking
more closely at a brain structure involved in motivation, called the
nucleus accumbens. This small region drives reward-seeking behaviors
underlying the pursuit of sex, recreational drugs like nicotine and
alcohol, and food.

"These brain motivation centers evolved to help us survive; finding
food and having sex are essential to the survival of an individual and
of a species," said Carrie Ferrario, Ph.D., associate professor in the Department of Pharmacology at U-M Medical School.

"What was advantageous when food was hard to find has become a
disadvantage and unhealthy in the current food dense environment. This is compounded by the over-abundance of over-processed, low nutrition foods
that may satisfy our taste but leave our bodies unnourished. People don't
tend to find it difficult to turn down an extra serving of broccoli,
but just one more french-fry or making room for a bit of chocolate dessert...that's a different story. The real challenge is overcoming these urges and changing our behavior when it comes to food," Ferrario added.

Given the immense toll obesity takes on virtually all body systems,
Ferrario, Peter Vollbrecht, Ph.D., of Western Michigan University, and
their colleagues are using rat models to understand potential brain
differences between animals who are prone to over-eating and obesity
and those who are not.

Previous research from Ferrario's lab pinpointed differences in the
nucleus accumbens in obesity-prone and obesity-resistant rats. Their
latest study, published in the Journal of Neurochemistry, tracked what
was happening in real time in the brain when these animals were presented
with glucose, a type of sugar, labeled with a tracer. The tracer allowed
the researchers to measure this new sugar in the brain.

Sugar is the brain's main fuel source and once there, the molecule is
broken down and used to create new molecules such as glutamine, glutamate,
and GABA, each with an important role in influencing the activation of
neurons in the brain and nervous system.

"Glucose that is consumed gets broken down and then its carbons get incorporated into neurotransmitters. We see those labelled carbons showing
up in those molecules -- glutamate, glutamine, and GABA -- over time," explained Vollbrecht.

They found that glucose was taking longer to get into the nucleus
accumbens of obesity-prone animals.

Furthermore, when measuring the concentration of the glutamate,
glutamine, and GABA, they discovered excess levels of glutamate, an
excitatory neurotransmitter. This, said the team, implied a defect in a neurotransmitter recycling process, typically maintained in the nervous
system by star-shaped cells called astrocytes.

Normally, astrocytes will pull glutamate out of the space between neurons, called the synapse, convert it into glutamine, and then shuttle it back to cells that produce GABA or glutamate. This sequence is crucial for turning neurons off and on. "The findings suggest that we're getting too much
glutamate and it's not being taken out of the synapse," said Vollbrecht.

Ferrario added, "The balance between glutamate and GABA (the main
inhibitory transmitter) is really important for brain function and
will influence activity of the neurons in the nucleus accumbens." This balance, and therefore brain activity, is different in obesity-prone vs.

obesity-resistant rats.

The fact that these rats are either prone to obesity or not is important
for disentangling cause and effect, says Vollbrecht. "It allows us to
remove diet as one of the variables." The team hopes to next study the
role of inflammation in the development of obesity, and how differences
in brain function contribute to susceptibility and resistance to obesity.

* RELATED_TOPICS
o Health_&_Medicine
# Diet_and_Weight_Loss # Obesity # Nervous_System #
Nutrition
o Mind_&_Brain
# Dieting_and_Weight_Control # Nutrition_Research #
Neuroscience # Brain_Injury
* RELATED_TERMS
o Blood_sugar o Sugar o Positron_emission_tomography o
Sugar_substitute o Brain o Diabetes o Honey o Brain_damage

========================================================================== Story Source: Materials provided by
Michigan_Medicine_-_University_of_Michigan. Original written by Kelly
Malcom. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Peter J. Vollbrecht, Kathryn M. Nesbitt, Victoria M. Addis,
Keenan M.

Boulnemour, Daniel A. Micheli, Kendall B. Smith, Darleen
A. Sandoval, Robert T. Kennedy, Carrie R. Ferrario. Differential
regulation of nucleus accumbens glutamate and GABA in
obesity‐prone and obesity‐resistant rats. Journal of
Neurochemistry, 2022; DOI: 10.1111/jnc.15720 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/02/230202153602.htm

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