Writing in Nature Metabolism, the research team suggests that the high rate of weight regain after successful weight loss may be due to a resistance to the nutrient signals generated after food consumption.
“We show that a 12-week supervised dietary intervention promotes significant weight loss and metabolic improvement but does not restore the physiological brain response to post-ingestive glucose or lipids in humans with obesity, at least during the time course of this study,” the study reads.
“Whether these systems are restored with long-term weight loss remains to be determined. Unfortunately, in practice, it may never come to this, because most patients regain weight within a few years of dieting.
“If shown to be true, this would make these impairments even more appealing therapeutic targets, not only for weight loss but also for weight maintenance.”
Amsterdam UMC and Yale University researchers’ results
Results from the single-blinded, randomised, controlled crossover study found that glucose and lipid infusions caused oral sense-independent nutrient-specific brain activity and striatal dopamine release in a group of 28 lean participants.
In contrast, a group of 30 obese participants showed severely impaired brain responses to post-ingestive nutrients.
"Our findings suggest that long-lasting brain adaptations occur in individuals with obesity, which could affect eating behaviour,” said Mireille Serlie, lead researcher and professor of endocrinology at Amsterdam UMC.
“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.
“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.”
Gut–brain axis signalling role in weight loss and gain
In an accompanying editorial comment, Mary Elizabeth Baugh, PhD, and Alexandra G DiFeliceantonio, PhD, from the Fralin Biomedical Research Institute at Virginia Tech Carilion in the US, emphasised that post-ingestive signalling pathways for proteins may be even more complex.
“Future work that explores the post-ingestive effects of proteins across different metabolic profiles will be needed to create a more complete understanding of gut–brain signalling,” they wrote.
“Given the ubiquity of weight regain after behavioural weight loss, this study also provides a fertile foundation for future work to explore how gut–brain axis signalling may influence weight loss maintenance and weight regain.
“Whether differences in post-ingestive nutrient-induced responses differ between ‘responders’ and ‘non-responders’ to clinical weight loss treatments is an important avenue of research.”
Also commenting on the implications of the study findings was Naveed Sattar, professor of metabolic medicine at University of Glasgow, who pointed out that brain adaptations may take time.
“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,” he said. “They may be, but more work is needed to confirm.”
Study methods
Twenty-eight lean participants with body mass index (BMI) under 25 kg/m2 and 30 participants with obesity and BMI over 30 kg/m2 were included in the analysis.
The research team measured their brain activity using MRI and dopamine release via single-photon emission computed tomography (SPECT) scans.
While the participants with a healthy bodyweight displayed specific patterns of brain activity and dopamine release after nutrient infusion (either 500 kcal of glucose or lipid), these responses were blunted in participants with obesity.
Additionally, 10% body weight loss (following a 12-week diet) was not sufficient to restore these brain responses in individuals with obesity, suggesting that 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,” concluded Serlie.
