Researchers at the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, in collaboration with the German Center for Diabetes Research, have found that a short-term, high-caloric diet impairs brain insulin responsiveness and increases liver fat in healthy weight men, with effects extending beyond the consumption period.

They also found disruptions in the brain's normal reward learning response, suggesting that just five days of overeating could prime the brain for long-term unhealthy eating patterns.

Insulin resistance in the brain is associated with obesity, type 2 diabetes, and cognitive dysfunction. Insulin normally regulates appetite and metabolism through brain signalling, but resistance in this pathway can disrupt these processes, potentially contributing to obesity and related diseases.

In the study, "A short-term, high-caloric diet has prolonged effects on brain insulin action in men," published in Nature Metabolism, the team investigated the short-term effects of an ultra-processed, high-caloric diet on brain insulin action before significant weight gain occurs. Julian Nowogrodzki authored a News article on the research that was published in Nature.

Twenty-nine healthy male participants aged 19–27 years (BMI 19–25 kg/m²) were assigned to either a high-caloric diet (HCD) group (n=18) or a control group (n=11). Over five days, the HCD group attempted to consume an additional 1,500 kcal daily from ultra-processed snacks while the control group maintained their regular diet. Physical activity restrictions during the study limited participants to under 4,000 steps per day.

Participants in the HCD group increased their daily caloric intake by an average of 1,200 kcal during the intervention. Liver fat content significantly rose from 1.55% ± 2.2% at baseline to 2.54% ± 3.5% post-intervention, with no change in the control group. No significant differences emerged in body weight, peripheral insulin sensitivity, or inflammatory markers.

Brain insulin responsiveness was assessed through functional magnetic resonance imaging (fMRI) combined with intranasal insulin administration at three visits: baseline, immediately post-intervention, and one week after resuming a regular diet. Additional measures included liver fat quantification via MR spectroscopy, body composition, oral glucose tolerance tests, and behavioural assessments.

Brain insulin responsiveness increased post-HCD in the right insular cortex, left rolandic operculum, and right midbrain/pons. One week after resuming a regular diet, insulin activity was significantly lower in the right hippocampus and bilateral fusiform gyrus.

Changes in brain insulin responsiveness correlated with liver fat accumulation and dietary fat intake. No significant differences in hypothalamic insulin response were found. Persistent reductions in brain insulin responsiveness in cognitive regions were noted.

White matter integrity, measured through diffusion tensor imaging, showed lower fractional anisotropy in major tracts, including the inferior frontal-occipital fasciculus and genu of the corpus callosum, at the one-week follow-up in the HCD group.

One of the more intriguing findings of the study was how a short-term HCD impacted reward learning, a cognitive process that influences motivation and decision-making. Reward learning relies on the brain's ability to associate certain behaviours with positive or negative outcomes, which plays an active role in food-related choices. Disruptions in this pathway have been widely observed in individuals with obesity, often resulting in altered eating behaviours and a heightened preference for calorie-dense foods.

To assess reward processing, participants completed a go/no-go reinforcement learning task designed to measure sensitivity to rewards and punishments. This task tests how well individuals learn to approach (go) or avoid (no-go) certain cues associated with positive (reward) or negative (punishment) outcomes. Performance in this task reflects how effectively the brain processes and adapts to feedback, which is crucial for regulating eating behaviour.

After just five days of consuming calorie-rich, ultra-processed snacks, participants in the HCD group showed decreased reward sensitivity and increased punishment sensitivity. This suggests that participants found rewarding outcomes less motivating and gained a heightened reaction to punishments. Effects trended toward baseline after returning to a regular diet for one week but did not fully reverse.

These short-term changes resemble obesity-related patterns but were observed here in healthy-weight men following a brief HCD.

More information: Stephanie Kullmann et al, A short-term, high-caloric diet has prolonged effects on brain insulin action in men, Nature Metabolism (2025). DOI: 10.1038/s42255-025-01226-9

Julian Nowogrodzki, How a junk-food splurge can change your brain activity, Nature (2025). DOI: 10.1038/d41586-025-00549-7

© 2025 Science X Network

--Justin Jackson , Medical Xpress