Why Most People Regain Lost Weight? Obesity Severely Impairs the Brain’s Response to Nutrients

Diminished Cognition Brain fMRI Concept

New research indicates that brain responses to nutrients are diminished in people with obesity and don’t improve even after weight loss. The study revealed that individuals with obesity released less dopamine in a brain region crucial for food intake motivation, compared to those with healthy body weight. Additionally, obese participants showed reduced brain activity upon nutrient infusion into the stomach. The lack of brain response improvement after weight loss could explain why most individuals regain weight after initial successful weight loss, the researchers concluded.

A joint study by Amsterdam UMC and Yale University reveals that obesity is linked to a diminished brain response to nutrients, which persists even after weight loss. This diminished response, which involves lower dopamine release and reduced nutrient-sensing activity, may contribute to the difficulty in maintaining weight loss.

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 University Medical Centers (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 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 a healthy body weight. 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 body weight 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 body weight 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 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.

For more on this study, see Yale Study Finds Severely Impaired Response to Nutrients.

Reference: “Brain responses to nutrients are severely impaired and not reversed by weight loss in humans with obesity: a randomized crossover study” by Katy A. van Galen, Anouk Schrantee, Kasper W. ter Horst, Susanne E. la Fleur, Jan Booij, R. Todd Constable, Gary J. Schwartz, Ralph J. DiLeone and Mireille J. Serlie, 12 June 2023, Nature Metabolism.
DOI: 10.1038/s42255-023-00816-9

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