By Catharine Paddock PhD

Fact checked by Jasmin Collier

The brain has complex circuitry that locks appetite to memories of finding and enjoying food. This drives the feeding behaviors necessary for survival. New research reveals that the circuits include one mechanism that does the opposite: curbing the compulsion to eat in response to food.

Once, scientists thought that gut instincts drove animals’ feeding behavior with very little input from the brain.

The sight and smell of food, they maintained, was enough to trigger eating.

However, since then, more and more evidence has suggested that the braindoes intervene to perform some decision-making about whether to proceed with eating or not.

What is less clear is which nerve cells are involved.

Now, researchers at The Rockefeller University in New York City, NY, have found a group of nerve cells, or neurons, whose activation reduces food intake.

They believe that their finding is the first to identify the mechanism, which they suggest acts as a “checkpoint” between detecting and consuming food.

The mechanism centers on dopamine 2 receptor (hD2R) neurons in the hippocampus, a brain structure that has a role in memory formation and the regulation of emotions.

A paper that now features in the journal Neuron describes how the team studied the cells and their effect on feeding behavior in mice.

The study also reveals that hD2R neurons are involved with memory and confirms that they form part of the complex brain circuitry that regulates eating.

“These cells,” explains first study author Estefania P. Azevedo, a postdoctoral researcher in the Laboratory of Molecular Genetics, “keep an animal from overeating.”

“They appear to make eating less rewarding and, in that sense, are tuning the animal’s relationship to food,” she adds.

Obesity and its consequences

According to the World Health Organization (WHO), more deaths globally are linked to overweight and obesity than to underweight. Since 1975, the number of people worldwide with obesity has tripled.

The WHO attribute this crisis to the rising consumption of energy-dense, high-fat food at the same time that lifestyles and jobs have become less physically demanding. The result is an upset in energy balance that favors weight gain.

National survey figures from 2013–2014 — which the National Institutes of Health (NIH) use in their reports — show that overweight or obesity affects more than two-thirds of adults in the United States. The survey also found that about 1 in 6 children and teenagers aged 2–19 years have obesity.

Overweight and obesity can have serious health consequences. They can raise the risk of high blood pressure, heart attack, stroke, and other cardiovascular conditions. Cardiovascular disease was the leading cause of death worldwide in 2012.

Carrying too much weight can also increase the risk of some cancers and make it more likely that disabling conditions that impair the joints, such as osteoarthritis, will develop.

Children with obesity are more likely to have obesity and disability and die prematurely as adults. They are also more likely to develop respiratory problems, fractures, high blood pressure, and show early signs of cardiovascular disease.

Understanding how the brain impacts eating

Treatments for overweight and obesity usually focus on changing lifestyle and habits in order to lose weight. These changes include adopting healthful eating patterns and increasing physical activity.

However, lifestyle changes may not be enough to help some people lose weight and keep it off. Doctors need to consider additional aids to weight loss, including drugs and surgery.

Gaining a better understanding of the brain circuits that control eating impulses could help improve such treatments.

Dr. Azevedo and her colleagues found that mice’s hD2R neurons influenced their feeding behavior. When the researchers stimulated the cells, the mice ate less food, and when they silenced them, the animals ate more food.

Speculating on the evolutionary advantage of such a circuit, Dr. Azevedo suggests that there could be times when not eating benefits survival. For example, shortly after a large meal, foraging for food could needlessly expose animals to predators.

But how do the hD2R neurons influence processes that help animals remember food locations? To investigate, the team stimulated the mice’s hD2R neurons as they explored an environment that was full of food.

The results revealed that hD2R neuron stimulation caused the mice to return less often to locations where they had found food. This suggests that the cells weaken memories about meals and their locations.

The team also investigated how hD2R neurons link to other brain circuits. They found that the cells receive messages from the entorhinal cortex, which is a brain region that processes signals from the senses. The cells also send messages to the septal area, which plays a role in controlling feeding behavior.

The researchers therefore suggest that the brain “fine-tunes” appetite by balancing memory-related mechanisms for promoting and restraining eating.