A new study published in Nature Metabolism suggests that even a short period of eating loads of sweet and fatty snacks can cause brain changes reminiscent of those seen in obesity and type 2 diabetes [1].
What can go wrong in five days?
If you usually eat healthy and take care of your body, there’s no harm in letting your guard down for a while, right? Not so fast, says a new study by the University Hospital of Tübingen, the German Center for Diabetes Research (DZD), and Helmholtz Munich.
This controlled but not randomized study recruited 29 young, healthy men with a normal body mass index (BMI). At baseline, there was no significant difference between the study group and the control group in terms of calories and nutrients consumed. Participants in the study group were asked to increase their daily calorie intake by 1,500 calories for five days by consuming highly processed sweet and fatty snacks. The researchers measured various biomarkers at baseline, after five days of the experiment, and one more week later.
Altered insulin responses
They found that even though body mass did not significantly change in the study group compared to controls, the unhealthy diet caused a noticeable increase in liver fat contents. Probably more intriguing results related to how the participants’ brains reacted to this ‘food assault.’ While insulin directly stimulates glucose uptake in muscle and fat cells, its role in the brain is different: it helps regulate appetite, metabolism, and cognitive functions related to food choices. The “brain first” hypothesis postulates that those reactions play an important role in the development of insulin resistance and related metabolic disorders.
Immediately after the five days of the experiment, the study group showed increased insulin responses in reward-related brain regions (insula, midbrain). This pattern has been previously observed as an early response to overeating [2] – conceivably, to make food less attractive. However, if the system “overshoots,” the dampened reward response might cause the person to eat more to get to the same level of satisfaction. The changes in the reward and punishment responses were evident in a series of cognitive experiments that the researchers conducted.
Some researchers suggest that heightened insulin activity could eventually lead to insulin resistance if healthy eating habits are not restored, though this remains to be confirmed. Indeed, in this study, one week after resuming a normal diet, the brain insulin responsiveness of the hippocampus and fusiform gyrus was reduced in the study group. These two brain regions are important for memory and cognition, including food-related decision-making. Earlier studies have found comparable reductions in brain insulin responsiveness in people with obesity and type 2 diabetes [3].
“Our findings demonstrate for the first time that even a brief consumption of highly processed, unhealthy foods (such as chocolate bars and potato chips) causes a significant alteration in the brain of healthy individuals, which may be the initial cause of obesity and type 2 diabetes,” said Dr. Stephanie Kullmann, the study’s lead author. “Interestingly, in our healthy study participants, the brain shows a similar decrease in sensitivity to insulin after a short-term high calorie intake as in people with obesity. This effect can even be observed one week after returning to a balanced diet.”
Is it “brain first”?
While the participants in the study group did return to their normal eating habits, this might be because they knew they were temporarily overeating as part of an experiment, not as a personal choice. This awareness likely made it easier for them to consciously give up overeating. People who start overeating in less controlled settings, such as in emotional distress, might not be so lucky.
Importantly, the researchers did not find signs of impaired peripheral insulin signaling, suggesting that brain insulin dysfunction may occur before systemic changes. This finding is in line with the “brain first” hypothesis, which suggests that brain insulin resistance may precede whole-body metabolic dysfunction. However, more rigorous studies are needed to confirm or disprove this.
The study had several important limitations, such as the small sample size and short follow-up duration. The scientists chose to limit participation to males because previous research has shown differences in insulin dynamics in males and females. However, this also affected the study’s generalizability and interpretability.
Dr. Andreas Birkenfeld, the study’s co-author, concluded, “We assume that the brain’s insulin response adapts to short-term changes in diet before any weight gain occurs and thus promotes the development of obesity and other secondary diseases.”
Literature
[1] Kullmann, S., Wagner, L., Hauffe, R., Kühnel, A., Sandforth, L., Veit, R., … & Birkenfeld, A. L. (2025). A short-term, high-caloric diet has prolonged effects on brain insulin action in men. Nature Metabolism, 1-9.
[2] Wingrove, J. O., O’Daly, O., Forbes, B., Swedrowska, M., Amiel, S. A., & Zelaya, F. O. (2021). Intranasal insulin administration decreases cerebral blood flow in cortico‐limbic regions: A neuropharmacological imaging study in normal and overweight males. Diabetes, Obesity and Metabolism, 23(1), 175-185.
[3] Arnold, S. E., Arvanitakis, Z., Macauley-Rambach, S. L., Koenig, A. M., Wang, H. Y., Ahima, R. S., … & Nathan, D. M. (2018). Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nature Reviews Neurology, 14(3), 168-181.