Even a brief period of overeating high-calorie foods may trigger liver fat accumulation and disrupt brain insulin action in healthy-weight men, with effects persisting beyond the time frame of the diet itself, according to findings from a recent report.
Researchers from the University of Tübingen and other German institutions found that these brain changes occurred without any detectable alterations in body weight or peripheral insulin sensitivity, suggesting that brain response to insulin can adapt to short-term dietary changes before weight gain occurs.
"We postulate that the brain response to insulin adapts to short-term changes in diet before weight gain and may facilitate the development of obesity and associated diseases," wrote lead study author Stephanie Kullmann, PhD, and colleagues in Nature Metabolism.
Researchers enrolled 29 healthy-weight male volunteers (age = 19–27 years, body mass index = 19–25 kg/m²) into the study, using a nonrandomized controlled design. Eighteen participants consumed a high-caloric diet (HCD) for 5 days, increasing their daily caloric intake by approximately 1,200 kcal with ultraprocessed snacks rich in sugar and saturated fat, while 11 participants maintained their regular diet throughout the study period.
Brain insulin responsiveness was assessed via functional magnetic resonance imaging (fMRI) combined with intranasal insulin administration at baseline, immediately after the 5-day intervention, and again 7 days after returning to a regular diet.
The results demonstrated that immediately following the HCD, participants randomized to the HCD arm exhibited significantly higher insulin activity in the right insular cortex, left rolandic operculum, and right midbrain/pons regions compared with the control group. One week after resuming their regular diet, the HCD group showed significantly lower brain insulin activity in the right hippocampus and bilateral fusiform gyrus.
"Liver fat content, however, substantially increased after this HCD, which was directly related to the initially augmented response to brain insulin of food reward pathways," the researchers noted.
The HCD also disrupted reward learning, as indicated by decreased sensitivity to rewards and increased sensitivity to punishments. The researchers also found reductions in white matter integrity between reward and cognitive brain regions in the HCD group after participants resumed their regular diet, similar to changes observed in individuals with obesity.
Previous research has established that brain insulin responsiveness is linked to long-term weight gain and unhealthy body fat distribution. People with aberrant insulin response have higher visceral adipose tissue mass and impaired peripheral metabolism.
This study is among the first to demonstrate that even short-term dietary indulgence can have lasting effects on brain insulin action—effects that persist after cessation of the unhealthy nutritional stimulus and before any detectable changes in body weight or peripheral insulin sensitivity.
"These data suggest that a short-term HCD, rich in sugar and saturated fat, has prolonged effects on the brain that outlast the time frame of its consumption," the researchers concluded.
The findings add new understanding to how unhealthy diets might contribute to the development of obesity and associated metabolic disorders.
Disclosures can be found in the study.