Two studies in rats indicate that the brains of obesity-prone animals process sugar differently and have reduced function of the brake signal. These findings provide new insights into what causes obesity.
About four in 10 Americans (41.9%) have obesity. Many factors, including an unhealthy diet, low physical activity levels, and insufficient sleep, can contribute to the development of this complex condition. Having certain illnesses and taking medicines may also lead to weight gain.
While lifestyle-related causes can cause the stigmatization of people with obesity, new research suggests that there may be little personal responsibility for overeating.
In the first study, researchers from the University of Michigan Medical School looked at potential brain differences between obesity-prone and obesity-resistant rats.
Previous research from the same team suggests that animals prone to overeating and obesity and those who are not had differences in the nucleus accumbens, a brain structure involved in motivation. This brain region also drives reward-seeking behaviors underlying the pursuit of food.
In their latest study, published in the Journal of Neurochemistry, researchers tracked what was happening in the brain when these rats were presented with glucose labeled with a tracer. This tracer measured new sugar in the brain in real-time.
Once in the brain, a sugar molecule is broken down and used to create new molecules such as glutamine, glutamate, and GABA, each of which helps to activate neurons in the brain and nervous system.
The research found that glucose took longer to reach the nucleus accumbens of obesity-prone animals. In addition, these rats had excess levels of glutamate, an excitatory neurotransmitter.
According to the researchers, this could imply a defect in a neurotransmitter recycling process, leading to getting too much glutamate.
The study demonstrates that the balance between glutamate and GABA, 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 Peter Vollbrecht, Ph.D., a professor at Western Michigan University. "It allows us to remove diet as one of the variables."
Turning off the brain’s brake signal
A second study from the University of Calgary published in the journal Nature Neuroscience found that obese mice have a reduction in the function of the brain’s brake signal located in the lateral orbitofrontal cortex, a region involved in decision-making about rewards.
When researchers "turned off" the brake signal, lean mice continued to work for sucrose, a sugar component, even though they just consumed enough to be fully sated.
At the same time, when normal activity was restored in the orbitofrontal cortex of obese mice, they were able to control their eating habits.
Stephanie Borgland, Ph.D., a professor at the Cumming School of Medicine and senior author of the study said, "Our research is confirming that overeating has nothing to do with personal responsibility. It has to do with changes in the way the brain works in response to our food environment."
- Journal of Neurochemistry. Differential regulation of nucleus accumbens glutamate and GABA in obesity-prone and obesity-resistant rats.
- Michigan Medicine. Sugar is processed differently in the brains of obesity-prone vs. obesity-resistant rats.
- Centers for Disease Control and Prevention. Adult Obesity Facts.
- Centers for Disease Control and Prevention. Causes of Obesity.
- Nature Neuroscience. Disinhibition of the orbitofrontal cortex biases decision-making in obesity.