Molecular evidence points to neural underpinnings of obesity – ScienceDaily

On diet? Maybe you’re avoiding sweets or carbs altogether, or curbing late-night binge eating. These are examples of behavior changes and when it comes to food, these diet triggers can be quite difficult to avoid.

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

“These brain motivational centers evolved to help us survive; Finding food and having sex are critical to the survival of an individual and a species,” said Carrie Ferrario, Ph.D., associate professor in the Department of Pharmacology at UM Medical School.

“What was beneficial when food was hard to find has become a disadvantage and unhealthy in today’s food-rich environment. Add to this the overabundance of over-processed, nutrient-poor foods that can satisfy our tastes but leave our bodies starved. People don’t find it difficult to turn down an extra helping of broccoli, but just one more fries or making room for some chocolate dessert…that’s another story. The real challenge is overcoming that urge and our eating behaviors to change,” added Ferrario.

Given the immense toll obesity takes on virtually all body systems, Ferrario, Peter Vollbrecht, Ph.D., of Western Michigan University, and their colleagues use rat models to understand potential brain differences between animals that are prone to overeating and obesity and those who aren’t.

Previous research from Ferrario’s lab revealed differences in the nucleus accumbens in obesity-prone and obesity-resistant rats. Their latest study, published in the Journal of Neurochemistry, tracked in real time what was happening 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 it gets there, the molecule is broken down and used to create new molecules like glutamine, glutamate, and GABA, each of which has an important role in affecting the activation of neurons in the brain and nervous system play.

“Ingested glucose is broken down and then its carbons are incorporated into neurotransmitters. We see these labeled carbons appearing in these molecules — glutamate, glutamine, and GABA — over time,” Vollbrecht explained.

They found that in obese-prone animals, glucose took longer to get into the nucleus accumbens.

Additionally, when they measured levels of glutamate, glutamine, and GABA, they discovered excessive levels of glutamate, an excitatory neurotransmitter. This, the team says, suggests a defect in a neurotransmitter recycling process typically maintained in the nervous system by star-shaped cells called astrocytes.

Normally, astrocytes pull glutamate from the space between neurons called synapses, convert it to glutamine, and then transport it back to cells that produce GABA, or glutamate. This sequence is crucial for turning neurons on and off. “The results suggest that we’re getting too much glutamate and it’s not being taken out of the synapse,” Vollbrecht said.

Ferrario added: “The balance between glutamate and GABA (the main inhibitory transmitter) is really important for brain function and will affect the activity of the neurons in the nucleus accumbens.”

This balance, and hence brain activity, is different in obesity-prone rats than in obesity-resistant rats.

The fact that these rats are either prone to obesity or not is important to unraveling cause and effect, Vollbrecht says. “It allows us to remove diet as one of the variables.”

The team hopes to next study the role of inflammation in causing obesity and how differences in brain function contribute to susceptibility and resistance to obesity.

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