This shows a brain.
The subjects with obesity also showed reduced responsivity in brain activity upon infusion of nutrients into the stomach. Credit: Neuroscience News

Obesity and the Brain: Stubborn Dopamine Responses Hamper Weight Loss

Summary: The brain responses to specific nutrients are significantly diminished in individuals with obesity, even after weight loss.

The study found that those with obesity released less dopamine in areas of the brain crucial for food intake motivation, compared to their healthy-weight counterparts. Furthermore, these subjects exhibited reduced brain activity upon nutrient infusion into the stomach.

These findings suggest long-lasting brain adaptations in obesity that could potentially influence eating behavior and weight management.

Key Facts:

  1. Individuals with obesity demonstrated diminished dopamine release in areas of the brain that regulate the motivational aspects of food intake.
  2. Brain activity in response to nutrient infusion in the stomach was significantly lower in individuals with obesity.
  3. Even after a 10% body weight loss, the altered brain responses in obese individuals did not restore to normal, hinting at persistent brain adaptations linked to obesity.

Source: University of Amsterdam

Brain responses to specific nutrients are diminished in individuals with obesity and are not improved after weight loss, according to a study led by Amsterdam UMC and Yale University, published today in Nature Metabolism.  

“Our findings suggest that long-lasting brain adaptations occur in individuals with obesity, which could affect eating behaviour.

“We found that those with obesity released less dopamine in an area of the brain important for the motivational aspect of food intake compared to people with a healthy bodyweight. Dopamine is involved in the rewarding feelings of food intake.  

“The subjects with obesity also showed reduced responsivity in brain activity upon infusion of nutrients into the stomach.

“Overall, these findings suggest that sensing of nutrients in the stomach and gut and/or of nutritional signals is reduced in obesity and this might have profound consequences for food intake.” says Mireille Serlie, lead researcher and Professor of Endocrinology at Amsterdam UMC. 

Food intake is dependent on the integration of complex metabolic and neuronal signals between the brain and several organs, including the gut and nutritional signals in the blood. This network triggers sensations of hunger and satiation, regulates food intake as well as the motivation to look for food.

While these processes are increasingly better understood in animals, including in the context of metabolic diseases such as obesity, much less is known about what happens in humans. Partly due to the difficulty in designing experimental setups in the clinic that could shed light on to these mechanisms.  

In order to address this lack of knowledge, Serlie, who is also a professor at Yale, and colleagues from both institutions designed a controlled trial.

This trial consisted of infusing specific nutrients directly into the stomach of 30 participants with a healthy bodyweight and 30 individuals with obesity, while simultaneously measuring their brain activity through the use of MRI and dopamine release using SPECT scans.  

While the participants with a healthy bodyweight displayed specific patterns of brain activity and dopamine release after nutrient infusion, these responses were severely blunted in participants with obesity.

Moreover, 10% body weight loss (following a 12-week diet) was not sufficient to restore these brain responses in individuals with obesity, suggesting long-lasting brain adaptations occur in the context of obesity and remain even after weight loss is achieved.  

“The fact that these responses in the brain are not restored after weight loss, may explain why most people regain weight after initially successful weight loss,” concludes Serlie.  

About this obesity and dopamine research news

Author: Jack Cairns
Source: University of Amsterdam
Contact: Jack Cairns – University of Amsterdam
Image: The image is credited to Neuroscience News

Original Research: Closed access.
Brain responses to nutrients are severely impaired and not reversed by weight loss in humans with obesity: a randomized crossover study” by Mireille Serlie et al. Nature Metabolism


Brain responses to nutrients are severely impaired and not reversed by weight loss in humans with obesity: a randomized crossover study

Post-ingestive nutrient signals to the brain regulate eating behaviour in rodents, and impaired responses to these signals have been associated with pathological feeding behaviour and obesity.

To study this in humans, we performed a single-blinded, randomized, controlled, crossover study in 30 humans with a healthy body weight (females N = 12, males N = 18) and 30 humans with obesity (females N = 18, males N = 12).

We assessed the effect of intragastric glucose, lipid and water (noncaloric isovolumetric control) infusions on the primary endpoints cerebral neuronal activity and striatal dopamine release, as well as on the secondary endpoints plasma hormones and glucose, hunger scores and caloric intake.

To study whether impaired responses in participants with obesity would be partially reversible with diet-induced weight loss, imaging was repeated after 10% diet-induced weight loss.

We show that intragastric glucose and lipid infusions induce orosensory-independent and preference-independent, nutrient-specific cerebral neuronal activity and striatal dopamine release in lean participants.

In contrast, participants with obesity have severely impaired brain responses to post-ingestive nutrients. Importantly, the impaired neuronal responses are not restored after diet-induced weight loss.

Impaired neuronal responses to nutritional signals may contribute to overeating and obesity, and ongoing resistance to post-ingestive nutrient signals after significant weight loss may in part explain the high rate of weight regain after successful weight loss.

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  1. I think it’s interesting how they say that doapamine levels are not restored after 10% weight loss because it seems to assume that one started off with normal levels. Maybe some people do.
    However, I would postulate that people who have a lifelong struggle with their weight never had enough – hence the problem with their weight.

    I would also be interested to see if there’s a corrolation or comorbidity with other dopamine deficient conditions like ADHD.

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