How Obesity Affects Brain Signals and Dopamine Production: Amsterdam Study in Nature Metabolism

In people who are obese, the brain responds less well to signals from the intestines. If they’ve lost weight, it won’t get any better. They don’t feel good that they’ve eaten yet, it turns out an Amsterdam study those this week Nature Metabolism popped up.

It was already known that the brain of obese people reacts differently when seeing pictures of food than the brain of slim people. But in addition to messages through the eye, mouth and nose, there is also communication between the gastrointestinal system and the brain. In mice that received a fat infusion, it has been shown that there is a link from the stomach and intestines to the release of dopamine in the brain. If mice are given too much sugar and fat, the mouse brain produces less dopamine in response to food.

Doctors at the Amsterdam UMC wanted to know whether that communication is also disrupted in humans. They gave 28 people with a healthy weight and 30 obese people fat and glucose (sugar) via a gastric tube. For example, the brain response was disconnected from the signals that go to the brain by smelling and tasting food, and it was possible to look purely at the effect from the stomach and intestines. Participants were also given water, to make sure the brain wasn’t just responding to a full stomach.

Dopamine

Two different scans showed activity in the brain. The researchers also looked at the release of dopamine, the messenger chemical that is produced in the reward center in the brain and gives a pleasant feeling. After the obese people had been on a diet for three months, it was examined whether weight loss had changed anything.

“In people with a healthy weight, we saw that different areas in the brain respond to sugar and fat. When we zoomed in on the reward center, which is important for appetite regulation, we also saw changes there,” says professor Mireille Serlie, internist-endocrinologist at Amsterdam UMC and at Yale University (US). In the obese people, we did not measure any change in brain activity, the reward center did not show any measurable response.

The striking thing was: even a 10 percent weight loss did not yield any improvement. “The brain does not register sufficiently that food has entered the stomach. As a result, you can easily eat too long or too much.” It’s like the reward center’s calorie sensor is turned off.

Fat is in a lot of our food

Mireille Serlie professor

The fact that the brain’s response to food in the stomach didn’t change after weight loss may be one of the reasons why it’s so hard to stay slim when you’ve lost a lot of weight, according to Serlie and her colleagues.

The researchers were also curious about dopamine release in obese people, as it is suspected that when it is disrupted, it contributes to the tendency to eat more than the body needs. What they saw: The sugar infusion released dopamine in the reward center in the brain in all groups. But with the fat infusion, that effect was only seen in the slim people. Obese people didn’t get that nice shot of dopamine when they got fat in their stomach and intestines. It could be, says Serlie, that obese people need to eat more to have the same effect on dopamine. Moreover, this process, which if it works well helps to stop eating in time, did not suddenly start when people had lost weight.

Lots of calories

Half of the Dutch population is overweight and about 80 percent of the products in the supermarket are too sweet, too salty and too fat. “Fat is in a lot of our food and provides a lot of calories per gram,” says Serlie. “It would be good to repeat the study with a combination of nutrients.”

Although more is now clear about the disrupted communication between the brain and the gastrointestinal tract in people with obesity, Serlie does not yet know whether or how this can be corrected. “For example, we also want to investigate whether the new obesity drugs are so successful because they improve the brain’s ability to register food in the stomach.”

The people in this study who had lost weight had a new brain scan immediately after twelve weeks of dieting. Serlie does not know whether brain activity will slowly recover in the long term. “This is also difficult to study because a majority of people who lose weight unfortunately gain it back.”