Losing weight and keeping it off involves more than willpower

Nearly 42% of adults across the US have obesity, according to the most recent reporting from the Centers for Disease Control and Prevention. And while size and poor health outcomes aren’t always connected, adults with obesity also have a much higher risk of developing type 2 diabetes, heart disease and other comorbidities linked to waist size.

The bad news doesn’t stop there, either. For those who do manage to lose weight, it’s unlikely to stay lost.

But a new study has found that it may not be a lack of willpower, but a lack of dopamine signaling in response to nutrients – something more prevalent in adults with obesity – that encourages behaviors like high-sugar food choices and chronic overeating.

“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,’” said Mireille Serlie, professor of medicine (endocrinology) at Yale School of Medicine and senior author of the study. “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.”

In the study, 28 lean adults (body mass index of 25 or less) and 30 adults with obesity (BMI of 30 or higher), had a glucose or fat infusion, and then a functional magnetic resonance imaging (fMRI) scan to measure brain activity.

Among the lean cohort, the scientists observed reduced activity across various regions of the brain, but there were no changes in the brains of the participants with obesity.

“This was surprising,” said Serlie. “We thought there would be different responses between lean people and people with obesity, but we didn’t expect this lack of changes in brain activity in people with obesity.”

It’s the latest in a growing body of evidence linking the gut and brain as key conspirators in weight management. The team looked specifically at the striatum, which is linked to the reward and motivation response to food intake. Here, one of the key regulators is the famous feel-good neurotransmitter, dopamine.

The study revealed that, in lean people, glucose and fat triggered a dopamine release, which regulated activity in two parts of the striatum. For the participants with obesity, fMRI revealed that their brains only responded to the glucose, and only in one section of the striatum. It failed to trigger any dopamine in response to the fat.

What’s more, the results were the same when the participants with obesity were tested after a 12-week diet, in which they were able to reduce their body weight by at least 10%.

The scientists believe this stunted nutrient sensing in adults with obesity, even after losing weight, makes it very challenging to not overeat in order to seek out that satiated, rewarded feeling that comes from the dopamine release.

“Everyone overeats at times,” said Serlie. “But it’s unclear why some people continue to overeat and others don’t.

“We need to find where that point is when the brain starts to lose its capacity to regulate food intake and what determines that switch,” she added. “Because if you know when and how it happens, you might be able to prevent it.”

While there’s still so little known about the underlying gut-brain link and how it can drive behaviors, this study shows how a breakdown in communication between the two powerhouses can make weight loss so much more difficult.

And if neural networks don’t possess the plasticity to rebuild once someone has lost weight, it may mean intervention is needed to help artificially trigger nutrient sensing in the striatum.

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

The research was published in the journal Nature Metabolism.

Source: Yale University