People With Obesity May Have 'Irreversible' Brain Changes

A new study found that individuals with obesity may have permanent changes in the brain's neuron responses to nutritional signals, impairing their ability to sense fullness and feel satisfied after eating specific foods.

Eating behavior is driven by a complex communication system between the brain, gut, and other organs. This system regulates feelings of hunger and the motivation to search for food and signals when the body is fed.

While obesity research involving animals has helped scientists understand these processes better, little is known about how they work in humans.


To learn more, researchers from Amsterdam University Medical Centers and Yale University recently investigated the brain responses to nutrients in people with obesity.

To conduct the study, published on June 12 in Nature Metabolism, the scientists recruited 30 people with obesity and 30 individuals with a healthy body weight. They then gave each participant an infusion of sugar, fat, or water. The researchers delivered each nutrient through a feeding tube to bypass the mouth so the participant couldn't discern the nutrient by smell, taste, or sight.

The night before testing, each participant ate the same food for dinner and did not eat again until the scientists placed the feeding tube.

The participants underwent single-photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI) while receiving each nutrient through the feeding tube.

The MRI showed researchers where the brain lit up in response to the nutrient, while the SPECT scan measured dopamine — a hormone that triggers feelings of pleasure and reward.

In participants with a healthy weight, the scans showed that ingesting fats or sugars slowed down signals in the stratum — a part of the brain that motivates people to find and consume food. This slowed signaling meant that the brain recognized the person was eating and the body was being fed. Simultaneously, dopamine levels increased with both fat and sugar, activating the reward centers in the brain.

In contrast, after sugar infusion, the brain scans of participants with obesity only showed slowing in one area of the stratum, while intake of fat did not change brain activity. Moreover, only sugar initiated a rise in dopamine.

To see whether weight loss would change or 'fix' these signals, the scientists had participants with obesity follow a 12-week diet to lose around 10% of their body weight.


After the participants lost weight, the scientists repeated the infusion/brain scan experiment.

They found that weight loss did not change or 'fix' the signaling in the brain. This suggests that these brain changes may be irreversible.

Scientists say these impaired responses to food signals may contribute to overeating and obesity. In addition, they remain unchanged even after weight loss, which might explain why people with obesity who successfully lose weight often regain it.

In a Yale press release, senior author Mireille Serlie, a professor of medicine (endocrinology) at Yale School of Medicine, says, "In my clinic, when I see people with obesity, they often tell me, 'I ate dinner. I know I did. But it doesn't feel like it.' And I think that's part of this defective nutrient sensing. This may be why people overeat despite the fact that they've consumed enough calories. And, importantly, it might explain why it's so hard to keep weight off."

Serlie also says these findings may help healthcare providers develop treatment plans that account for these brain changes. In addition, a future goal might be to find a way to restore nutrient sensing in people with obesity, if possible.

"People still think obesity is caused by a lack of willpower," explains Serlie. "But we've shown that there is a real difference in the brain when it comes to nutrient sensing."


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