New Study Reveals Persistent Impairment of Gut-Brain Responses to Nutrients in Individuals with Obesity, Even after Weight Loss

A recent study has uncovered significant findings that shed light on the complexity and lasting biological effects of obesity. Researchers have discovered that individuals with obesity experience impaired brain responses to nutrients in the gut, and these impairments persist even after weight loss achieved through dietary changes.

Using advanced brain imaging techniques, scientists observed that when individuals without obesity received nutrients, specific regions of their brain associated with food intake displayed reduced activity. This reduction indicated that the brain signaled that sufficient food had been consumed and that further intake was unnecessary. However, in individuals with obesity, these changes were not detected, as outlined in the study published in Nature Metabolism on Monday.

Traditionally, obesity has been regarded as a personal failure to consume less food, but there is a growing recognition that it stems from underlying biological mechanisms. This understanding has prompted the demand for new drugs like Wegovy, Ozempic, and Mounjaro, which have proven effective in helping individuals achieve significant weight loss.

The study contributes to the existing body of research that emphasizes obesity as “not simply a lack of willpower,” according to Mireille Serlie, senior author and a professor of medicine at Amsterdam University Medical Center and Yale University. Serlie further explained that individuals with obesity experience a misalignment between the sensing of food in the body and the brain’s response to it. This ongoing biological process elucidates why individuals struggle with obesity and find it challenging to maintain weight loss.

The study involved 28 participants without obesity (BMI under 25) and 30 participants with obesity (BMI over 30). The researchers directly infused tap water (as a control), glucose (sugar), and lipids (fats) into the stomachs of the participants to isolate the brain’s response to nutrients present in the stomach, without interference from visual, olfactory, or gustatory cues associated with food.

Using functional MRI, the researchers initially examined the overall brain responses and discovered reduced activity in regions responsible for regulating eating behavior in individuals without obesity, whereas no changes were observed in individuals with obesity. Zooming in on specific subregions of the brain involved in food intake (called the striatum), the researchers again found decreased activity in individuals without obesity but no changes in those with obesity.

Additionally, the researchers employed a different imaging method called SPECT to examine the release of dopamine, a neurotransmitter associated with food reward and motivation to eat. While sugar induced dopamine release in both groups, fats only elicited dopamine release in individuals without obesity, not those with obesity.

To investigate the reversibility of impaired brain responses, participants with obesity underwent a 12-week supervised diet program aimed at losing 10% of their body weight. However, when re-evaluated after this period, no differences in brain responses were observed, indicating that the impaired brain response in individuals with obesity cannot be swiftly reversed through dieting.

The researchers also explored the correlation between brain responses and gut hormones released during nutrient ingestion. While no association was found with insulin or glucose, the hormone glucagon-like peptide 1 (GLP-1) showed a correlation with reduced brain activity in certain areas related to food intake after fat infusion in individuals without obesity.

GLP-1 has attracted significant research interest due to its connection to popular drugs like Wegovy and Ozempic, which mimic its effects. Although the current study did not delve into the relationship between the GLP-1 hormone and brain responses, nor did it explore how GLP-1-based drugs affect individuals with obesity, these areas present potential avenues for further investigation, Serlie noted.