Vagus nerve stimulation sheds light on tackling obesity

F

or most people, and to their frustration, putting on weight is much easier than shedding pounds. But obesity is not a trivial matter. The condition affects all ages and socioeconomic groups and is not just a problem for rich countries.

According to the World Health Organization, over 155 million people suffer from obesity-related problems in the developing world. Excess weight can have serious consequences, including increasing the chances of chronic conditions such as type 2 diabetes and heart disease.

Tackling obesity is challenging. Plenty of studies have shown that diets simply don’t work for most people - or at least not in the long term. Many patients pile the weight back on again as soon as they stop their restrictive regime. Gastric band surgery is often the last resort for people facing serious health-related issues due to their weight.

The surgery has an impressive success rate - patients can lose up to 50% of their body weight in the first six months after the procedure. And research shows that a decade after surgery, most people maintain their new weight. However, the procedure is not for the faint-hearted. Surgeons make a small stomach pouch and reroute the digestive tract which can mean a long recovery period for patients.

Less intrusive options for treating obesity are clearly needed. In Nature Communications, researchers at Texas A&M University say they have developed a wireless, centimetre-sized device to treat obesity that, if approved in humans, would involve less time under the knife and a shorter recovery time than gastric band surgery.

The tiny implant works by stimulating the vagus nerve, the body’s neural ‘superhighway’, which connects the brain to the digestive system. Lead researcher Sung II Park, assistant professor in the electrical and computer engineering department at Texas A&M University, explains that the vagus nerve represents a possible target for treating obesity because it provides sensory information about fullness from the stomach lining to the brain. 

“If one can imitate the feeling of satiety or fullness, the desire to eat will be diminished,” he explains “We wanted to create a device that not only requires minimal surgery for implantation but also allows us to stimulate specific nerve endings in the stomach.”

Medical devices that stimulate vagus nerve endings and essentially zap the feeling of hunger away already exist. Some have even been approved by the FDA and look similar to a pacemaker, with wires connected to a current source providing electrical jolts to activate the tips of the vagus nerve in the stomach. What’s significant about Park’s device is that it is wireless.

He says it would be far less cumbersome and more comfortable for the patient than a wired implant. “Despite the clinical benefit of having a wireless system, no device, as of yet, has the capability to do chronic and durable cell-type specific manipulation of neuron activity inside of any other organ other than the brain,” he says.

Park’s project focuses on optogenetics, which involves the use of light to control physiology. The team used genetic tools in mice to express genes that respond to light in specific vagus nerve endings.

They then designed a small, paddle-shaped device containing micro-LEDs which was implanted in the animals’ stomachs. The implant also contains microchips that allow the device to communicate with an external radiofrequency source and tiny currents that power the LEDs.

When the radio frequency source was switched on, the researchers showed that the light from the LEDs was effective at reducing hunger in the mice. It suggests that light may be effective in mimicking a feeling of fullness in the stomach which, will tell the brain to suppress appetite.

This surprised Park and the team. It is widely accepted that when the stomach is full, it expands and the information about this stretching is conveyed to the brain via the vagus nerve.

“Our findings suggest that stimulating the non-stretch receptors, the ones that respond to chemicals in the food, could also give the feeling of satiety even when the stomach was not distended,” Park says.

In addition to implants, the team’s findings could assist other researchers in the search for medicines that treat obesity and excess appetite. Very few weight loss medications are currently on the market.

Orlistat, which works by preventing fat from food being absorbed by the body, is the only approved anti-obesity drug in the UK. However, a recent Phase III trial of diabetes drug semaglutide suggests that medicines designed to reduce food cravings may help us treat obesity in the near future. The study found semaglutide decreased cravings for high-fat foods and made people feel more in control over their appetite.

Park’s device is still in its early stages and has only been tested on mice so far. It will be several years before the technology can be trialled in humans. But the next stage for the Texas A&M team is to determine whether the device can suppress hunger for longer periods of time - potentially months.

That will involve experiments with obese mice to see if chronic activation of the vagal nerve endings in the stomach can reverse obesity. Park is working with leading neuroscientist Zachary Knight from the University of California, San Francisco to better understand the relationship between the vagus nerve and hunger.

“Wireless optogenetics and identifying peripheral neural pathways that control appetite and other behaviours are all of great interest to researchers in both the applied and basic fields of study in electronics, material science and neuroscience,” Park says.

“Our novel tool now enables interrogation of neuronal function in the peripheral nervous systems in a way that was impossible with existing approaches.”