Obesity weighs on the brain, impairs nutritional responses and thwarts diets

According to a study on human volunteers, conducted by researchers from UMC Amsterdam and Yale University, brain responses to specific nutrients are diminished in obese people and do not improve after weight loss. weight. The overall results may partly explain why many people regain weight even after a successful diet.

“Our results suggest that long-lasting brain adaptations occur in obese people, which could affect eating behavior,” said Mireille Serlie, MD, PhD, professor of endocrinology at UMC Amsterdam. “We found that obese people 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 gratifying sensations of food intake. Obese subjects also showed reduced responsiveness of brain activity when infusing nutrients into the stomach. Taken together, these results suggest that sensing of nutrients in the stomach and intestine and/or nutritional signals is reduced in obesity and this could have profound consequences for food intake… 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.

Serlie and his colleagues reported their findings in Natural metabolismin an article titled “Brain responses to nutrients are severely impaired and not reversed by weight loss in obese humans: a randomized crossover studyin which they concluded, “Altered neural responses to nutritional cues may contribute to overeating and obesity, and continued resistance to post-ingestive nutritional cues after significant weight loss may partly explain the high rate weight regain after successful weight loss.

Food intake depends on the integration of complex metabolic and neural signals between the brain and several organs, including the gut and nutritional signals in the blood. “…growing evidence points to a powerful role of signals that arise after food ingestion – so-called post-ingestive nutrient signals – in regulating eating behavior,” the authors noted. This network triggers feelings of hunger and satiety, regulates food intake as well as the motivation to seek food. But while these processes are increasingly understood in animals, including in the context of metabolic diseases such as obesity, much less is known about what happens in humans. “Despite these intriguing mostly preclinical studies, little is known about the role of post-ingestive nutritional signals in human physiology or the development of obesity,” they continued. This is partly due to the difficulty of designing clinical experimental setups that could shed light on these mechanisms.

To address this knowledge gap, Serlie, who is also a Yale professor, and his colleagues at both institutions designed a controlled trial. The study involved infusing specific nutrients directly into the stomachs of 30 participants with a healthy body weight and 30 obese people, while simultaneously measuring their brain activity through the use of MRI and dopamine release. using SPECT scanners. “…we hypothesized that intragastric glucose and lipid infusions modulate cerebral neuronal activity and striatal dopamine release in lean humans and that these responses are impaired in obese humans,” the authors said. researchers. Obese participants were studied before and after a dietary intervention aimed at reducing body weight by 10%. “…we hypothesized that an impaired response to post-ingestive nutritional cues is partially reversible with diet-induced weight loss,” the researchers added.

Their results showed that while participants with a healthy body weight displayed specific patterns of brain activity and dopamine release following nutrient infusion, these responses were severely attenuated in obese participants. Moreover, a 10% body weight loss (after a 12-week diet) was not sufficient to restore these brain responses in obese people, suggesting that long-lasting brain adaptations occur in the context of obesity and persist even after weight loss. “Taken together, these observations provide insight into the physiology of human eating behavior and the pathophysiology of obesity,” the researchers said.

The researchers said their collective findings support hypotheses that glucose and lipids differentially affect brain regions involved in regulating eating behavior through post-ingestive signals, and that altered post-ingestive nutrient signaling may contribute to pathological eating behavior, overeating and obesity. The persistence of these changes even after diet-induced weight loss may contribute to the high incidence of weight regain after dietary interventions. “The lack of reversibility after significant weight loss suggests that the high rate of weight regain after successful weight loss is partly explained by continued resistance to post-ingestive nutritional cues,” they wrote.

Write in an accompaniment News and Views, Mary Elizabeth Baugh, PhD, and Alexandra G. DiFeliceantonio, PhD, at the Franlin Biomedical Research Institute at VTC, Roanoke, pointed out that the reported study explored the post-ingestive effects of carbohydrates and lipids only, and that to create a With a more complete understanding of gut-brain signaling, future work will be needed to explore the post-ingestive effects of proteins. Nonetheless, they wrote, “Given the ubiquity of weight regain after behavioral weight loss, this study also provides a fertile foundation for future work to explore how gut-brain axis signaling may influence maintenance of weight loss and weight regain… That post-ingestive differences in nutrient-induced responses that differ between “responders” and “non-responders” to clinical weight loss treatments is one way important research. »