Could new discovery end obesity?

Researchers have identified certain neurons in the brain that regulate when to eat and when to stop eating—a mechanism that could potentially be used to curb obesity, according to results of a new study in Proceedings of the National Academy of Sciences.

“The bottom line is that we identified a new population of neurons, that when activated, suppress appetite and increase energy expenditure,” said lead investigator Baoji Xu, PhD, professor, Department of Neuroscience, Scripps Research Institute, Jupiter, FL.

The researchers also found that the opposite was true. When these neurons were deactivated or genetically deleted in a mouse model, the mice overate, reduced their level of activity, and started to become obese.

So, finding a way to activate the neurons’ appetite-suppressing, energy-activating ability may offer a new target for safe and effective obesity therapies, Dr. Xu noted.

Epidemic proportions

In recent years, obesity rates for both adults and children have climbed in the United States and worldwide. In 2015-2016, 39.8% of US adults (or 93 million) were considered obese, not counting 18.5% (13.7 million) of obese US children and teens, according to the Centers for Disease Control and Prevention.

But obesity isn’t a standalone problem; it’s linked to other health conditions including heart disease, stroke, type 2 diabetes, and certain types of cancer that may lead to preventable, premature death. In addition to the toll it takes on adults and children, obesity has economic costs, too. The estimated annual medical cost of obesity in the United States was $147 billion in 2008 US dollars. On an individual basis, the medical cost for a person with obesity was $1,429 higher than those of normal weight.

Due to this widespread and intractable problem, obesity has escalated from a public health crisis to a worldwide epidemic. Researchers, clinicians, and persons affected by obesity are all searching for a solution.

Obesity begins in the brain

For this study, Dr. Xu and his team began with the knowledge that in the brain, signaling between brain-derived neurotrophic factor (BDNF) and a certain receptor, TrkB, plays a critical role in the control of energy balance. They also knew that mutations in genes that express TrkB and BDNF have been associated with extreme obesity in humans and mice. What they didn’t know were which neurons in the brain express TrkB to control body weight.

To that end, the team used a mouse model to search in the dorsomedial hypothalamus—the same area of the brain where the hormone leptin binds to nerve cells to suppress appetite. It was here that they found the TrkB-expressing neurons that regulate food intake.

But they also discovered that the TrkB-binding neurons worked distinctly differently than the leptin-binding neurons. Leptin-binding neurons control feeding only during the night, when mice are hungry and search for food. However, when the researchers activated the TrkB-expressing neurons during the night, the mice ate less than usual. Then, when they blocked the TrkB neurons during the day, when mice are usually satiated, the mice ate more and more.

The researchers corroborated this effect by deleting the gene for the TrkB receptor, which led to overeating, reduced energy expenditure, and obesity in the mice.

Dr. Xu and his team determined that the TrkB-expressing neurons turn off at night, when mice are hungry, and turn on during the day, to suppress appetite and maintain satiety.

A drug that activates these neurons could be a therapeutic intervention for treating obesity, the authors concluded.

“We still need to understand this system in humans. Once we do, maybe we will find a way to suppress appetite and increase energy expenditure,” Dr. Xu said.

This research was supported by the National Institutes of Health.