How obese brains struggle to detect fat ingestion

2023-07-03 10:27:09

DECRYPTION – The mechanism identified by researchers could explain the inability of overweight people to regulate their daily food intake.

We often hear that the intestine is our “second brain”. It is not a coincidence. When we eat, the detection of nutrients by the digestive system induces changes in brain activity, in particular through the release of dopamine, a “pleasure” hormone that determines the motivation to eat. But, according to a study published in the journal Nature Metabolism by a collaboration between researchers in Amsterdam (Netherlands) and Yale University (United States), this brain response would be altered in people in a situation of obesity. “The study shows very clearly that we must stop seeing obesity in relation to people’s will, but rather as a real metabolic disease and perhaps also of a psychiatric nature”, comments Giuseppe Gangarossa, professor and researcher in neuroscience at Paris Cité University, which did not participate in the study.

During digestion, food from the stomach is transformed into nutrients (carbohydrates, fats and proteins) in the intestine. These nutrients pass into the blood and are carried to different organs, such as the muscles and the brain, which use them to function properly. The objective of the study was to mimic food consumption in people of normal weight or in a situation of obesity in order to compare brain responses to different nutrients.

For this, the researchers injected sugar (glucose) and fats (lipids) directly into the stomachs of the volunteers. They then assessed the induced neural activity using a brain imaging technique. “As the participants could not know when they received glucose or lipids, the researchers were able to see if the brain response was different depending on the nature of the nutrients without this response being influenced by sight, l ‘smell or taste’, deciphers Serge Luquet, research director at the CNRS and team leader in the functional and adaptive biology laboratory of the University of Paris Cité.

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Resistance to fat assimilation

First observation: several regions of the brain were less active in obese people and this depended on the nature of the nutrient. More specifically, the researchers focused on the area of ​​the brain that responds to the release of dopamine, the striatum. They found that the activation of this region by glucose was similar in obese and normal-weight people. On the other hand, in response to lipids, the release of dopamine, and therefore the activation of the striatum, was lower in obese people. “This dysfunction of the cerebral response to fats could be explained by an alteration of the neural circuits and a failure of the sensitivity of the dopamine receptors”, underlines Prof. Gangarossa.

To find out if the brain’s response can be restored by weight loss, overweight participants lost about 10% of their body mass over 12 weeks. However, no change was subsequently observed. The brain was still “resistant” to fat detection. “This is a major finding in the field as it would prove that the brain may lose its ability to regulate food intake through an adaptive or dopamine ‘resistance’ mechanism, specifically in response to fat consumption.” , explains Serge Luquet. Concretely, when an obese person consumes fat, the brain does not detect it, or rather in a defective way, so that they continue to eat. Such a dysfunction could explain why most people suffering from obesity are unable to lose weight over the long term.

But then, is it a reversible mechanism? “Throughout the disease, the brain finds itself bombarded by aberrant signals against which it fights. At some point it succumbs and ends up going wrong,” explains Giuseppe Gangarossa. According to the researchers, this disruption could be reversible but as it took place over several years, twelve weeks would have been insufficient to see a return to normal. Despite this, explains Serge Luquet, “the study provides an important piece of understanding of the mechanisms by which obesity can leave a lasting mark in the dialogue between the intestine and the brain”.

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