A short period of eating a high-calorie, ultra-processed diet can affect insulin action in the brain in ways that persist even after a return to a normal diet. These changes can contribute to the development of insulin resistance in the brain and potentially to obesity and other metabolic diseases. This reinforces the importance of maintaining a balanced diet and avoiding excessive consumption of ultra-processed foods, which can have long-lasting impacts on brain and metabolic health.
Insulin resistance is a common problem in people with obesity and type 2 diabetes. This condition affects not only the body, but also the brain. Normally, insulin in the brain helps to reduce hunger and control metabolism.
However, when there is insulin resistance, this function is compromised, which can lead to difficulties in weight control and even an increased risk of metabolic, psychiatric and neurodegenerative problems.
Although it is already known that insulin in the brain is linked to these processes, it is still unclear how this response develops over time.
To better understand this issue, researchers conducted a study to analyze how consuming a high-calorie diet rich in ultra-processed foods can affect the action of insulin in the brain.
The study involved 29 healthy men, ages 19 to 27, who were divided into two groups. One group followed their normal diet, while the other added 1,500 extra calories per day by consuming ultra-processed snacks for five days.
After this period, the participants in the high-calorie diet group returned to their regular diet for seven days, and the researchers monitored the changes in their bodies and brains during three time points: before the diet change, immediately after the five-day high-calorie diet, and one week after returning to their normal diet.
To measure the action of insulin in the brain, the researchers used a nasal insulin spray and functional magnetic resonance imaging (fMRI). This technique allowed them to observe how different brain regions responded to insulin before and after the high-calorie diet.
The results showed that immediately after the five days of high-calorie eating, some areas of the brain linked to food reward (such as the insular cortex and midbrain) showed greater activity in response to insulin.
This suggests that overconsumption of ultra-processed foods may increase the brain’s sensitivity to insulin in these regions, which may influence food cravings and eating behavior.
However, one week after returning to a normal diet, the researchers observed the opposite effect: insulin activity dropped in other areas of the brain, such as the hippocampus and fusiform gyrus, which are important for memory and learning.
This suggests that even after the diet returned to normal, the impact on the brain persisted. These changes may have long-term implications, as the hippocampus is essential for controlling eating and learning healthy habits.
In addition to changes in brain activity, the researchers also looked at the impact of the diet on the body. Although the participants did not gain significant weight in just five days, the group that consumed more calories showed an increase in fat accumulation in the liver.
This finding is concerning because excess fat in the liver is associated with a higher risk of insulin resistance and metabolic problems later in life.
Interestingly, the study found no significant differences in insulin sensitivity in the rest of the body, nor in markers of inflammation in the blood, such as C-reactive protein and interleukins.
This may indicate that brain changes occur before broader metabolic changes. Other studies have shown that people with obesity have altered insulin responses in areas of the brain linked to reward, which can lead to difficulties regulating appetite.
The new findings suggest that these changes may begin even before weight gain, meaning that overconsumption of ultra-processed foods can rapidly alter brain function, independent of immediate changes in peripheral metabolism.
The researchers also highlighted that other conditions, such as inflammation in the brain, may be involved in this process. Previous studies suggest that overeating can trigger inflammation in brain regions linked to appetite control, which can lead to a vicious cycle of increased hunger and difficulty regulating weight.
In the current study, participants who consumed the high-calorie diet showed changes in the integrity of the brain’s white matter, which may be indicative of inflammatory processes. However, more research is needed to better understand this relationship.
Although the study yielded important findings, it also has limitations. The number of participants was small, which makes it difficult to generalize the results. In addition, the research was conducted only with young, healthy men, so it is not known whether the same effects occur in women or in people with different health conditions.
The impact of different types of high-calorie foods, such as those rich in carbohydrates versus those rich in healthy fats, was also not analyzed.
In summary, the study showed that a short period of high-calorie, ultra-processed food can affect insulin action in the brain in ways that persist even after a return to a normal diet.
These changes may contribute to the development of insulin resistance in the brain and, potentially, to obesity and other metabolic diseases. This reinforces the importance of maintaining a balanced diet and avoiding excessive consumption of ultra-processed foods, which can have lasting impacts on brain and metabolic health.
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A short-term, high-caloric diet has prolonged effects on brain insulin action in men
Stephanie Kullmann, Lore Wagner, Robert Hauffe, Anne Kühnel, Leontine Sandforth, Ralf Veit, Corinna Dannecker, Jürgen Machann, Andreas Fritsche, Nobert Stefan, Hubert Preissl, Nils B. Nature Metabolism. 21 February 2025
DOI: 10.1038/s42255-025-01226-9–
Abstract:
Brain insulin responsiveness is linked to long-term weight gain and unhealthy body fat distribution. Here we show that short-term overeating with calorie-rich sweet and fatty foods triggers liver fat accumulation and disrupted brain insulin action that outlasted the time-frame of its consumption in healthy weight men. Hence, brain response to insulin can adapt to short-term changes in diet before weight gain and may facilitate the development of obesity and associated diseases.
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