Dopamine depletion: Obesity reduces brains responses to nutrients, study flags

14 Jun 2023 --- Researchers from Amsterdam University Medical Centers (UMC) and Yale University found that the brain responses of individuals with obesity are diminished to specific nutrients. The subjects showed reduced responsivity in brain activity when nutrients were infused into the stomach and not after weight loss either.

“These findings suggest that sensing of nutrients in the stomach and gut and 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. 

However, the study’s claims have been met with doubt by Naveed Sattar, professor of Metabolic Medicine, University of Glasgow. “This is very interesting work and but whether 12 weeks of weight loss is sufficient to change the stomach’s reaction to food or its shape and size is not known and such changes will influence the signals it sends to the brain.”   

Disrupted neural signals
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 and the motivation to look for food. 

According to this study, published in Nature Metabolism, 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. This is partly due to the difficulty in designing experimental setups in the clinic that could shed light on these mechanisms.

“Our findings suggest that long-lasting brain adaptations occur in individuals with obesity, which could affect eating behavior. 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 healthy body weight,” explains Serlie.

Dopamine is linked to the body’s food reward system.

Skeptical of the Nature Metabolism published findings, Sattar says brain adaptations may take time. Obese participants’ brain responsitivity was shown to be diminished.

“So, this work needs to be repeated in those who manage to maintain weight loss for at least six months to say the changes are long-lasting. They may be but more work is needed to confirm.”

Researchers from the Osaka Metropolitan University in Japan have also investigated what stimulates the brain to cause overeating and discovered a genetic mechanism associated with high-calorie, food-fueled obesity.

Closing the knowledge gap
The researchers of the present study are aware of the lack of information in this area of study. They designed a controlled trial whereby they infused nutrients directly into the stomach of 30 participants with healthy body weights and 30 individuals with obesity.

At the same time, they measured brain activity using magnetic resonance imaging scans and dopamine release using single-photon emission computed tomography scans.  

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

About 10% body weight loss (following a 12-week diet) was insufficient 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.  

Meanwhile, the World Obesity Federation predicts that by 2035, 51% of the world’s population will be overweight or obese if current patterns are unchanged. In its recently published Atlas report for 2023, the federation forecasts that the economic cost will hit US$4.3 trillion by 2035, which amounts to 3% of the global GDP and is on par with the financial impact of the COVID-19 pandemic in 2020.

Edited by Inga de Jong