Obesity impairs brain responses to nutrients, even after weight loss, study finds

Brain responses to nutrients in the gut are impaired in people with obesity, and that doesn’t change even after they lose weight through changes in diet, a new study finds, adding to mounting research showing the complexity and persistence of the biological effects of obesity.

Using brain imaging, researchers saw that when people without obesity received nutrients, they experienced reduced activity in areas of the brain involved in food intake, suggesting the brain is signaling to them that they’ve received food and no longer need more. But in people with obesity, those changes were not detected, according to the study published Monday in Nature Metabolism.

Obesity has long been framed as an individual’s failure to eat less, but there’s growing recognition that it’s rooted in biological mechanisms and that interventions like dieting aren’t effective in achieving long-term weight loss. That’s helped drive demand for new drugs, such as Wegovy, Ozempic, and Mounjaro, that have helped people shed significant amounts of weight.

This study adds to the literature showing obesity is “not just simply a lack of willpower,” said Mireille Serlie, senior author and a professor of medicine at Amsterdam University Medical Center and Yale University.

“The sensing of food being present in the body and the brain’s reaction to it is not in alignment in people with obesity,” she added. “There’s a biological process ongoing that really explains why people are struggling so much with obesity,” and why it’s hard to keep weight off.

The study included 28 people without obesity, defined as having a BMI under 25, and 30 people with obesity, defined as having a BMI over 30.

The researchers infused tap water (as a control), glucose (sugar), and lipids (fats) directly into participants’ stomachs, so they could look at how people’s brains responded solely from nutrients being present in the stomach, without distortion from any brain responses that come from looking, smelling, or tasting food.

The researchers first used functional MRI to look at responses in the brain generally, and found that people without obesity had reduced activity in regions that help regulate eating behavior, while no changes were found in people with obesity.

The researchers then zoomed in on specific subregions of the brain involved with food intake called the striatum, and they again saw decreased activity in people without obesity, but no changes in people with obesity.

Afterward, the researchers used a different imaging method called SPECT to look at the release of dopamine, which helps signal reward from food and is involved in the motivation to eat. While they found that sugar induced dopamine release in both groups, fats induced dopamine release only in people without obesity and not in people with obesity.

The participants with obesity then underwent 12 weeks of a supervised diet program to lose 10% of their body weight. When the researchers studied them again after that, they found no differences in their brain responses, suggesting that the impaired brain response in people with obesity can’t be quickly reversed by dieting.

The researchers also wanted to see if the brain responses were correlated with any hormones that are released when nutrients are in the gut. They didn’t find an association with insulin or glucose, but they did find that after infusion of fats in people without obesity, increased levels of the hormone glucagon-like peptide 1 (GLP-1) were correlated with reductions in brain activity in certain food intake-related areas.

GLP-1 has been a hot area of research, as the widely popular drugs Wegovy and Ozempic work by mimicking the effects of GLP-1. This study doesn’t delve into the relationship between the GLP-1 hormone and brain responses, nor does it look at how GLP-1-based drugs affect responses in people with obesity, but those could be areas of further research, Serlie said.

Paul Kenny, chair of the department of neuroscience at the Icahn School of Medicine at Mount Sinai who also researches the neurobiological mechanisms of obesity, said “all too often, people think that if you’re overweight, it’s really simple, just stop eating and you lose weight — problem solved. Papers like this get to the fact that it’s not so easy.”

“When you consume certain foods that result in weight gain, that can actually remodel the brain and how the brain works and those changes can be very long-lasting,” said Kenny, who was not involved in the new paper. “And those long-lasting changes presumably are influencing your choices regarding food in the future.”

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