“From Nutritional Patterns to Behavior: High-Fat Diet Influences on Inhibitory Control, Brain Gene Expression and Metabolomics in Rats”

Background Impulsive and compulsive behaviors are associated with inhibitory control deficits. Diet plays a pivotal role in normal development, impacting both physiology and behavior. However, the specific effects of high-fat diets (HFD) on inhibitory control have not received adequate attention. Objectives This study aimed to explore how exposure to an HFD from postnatal day (PND) 33 to PND77 affects impulsive and compulsive behaviors. Methods The experiment involved 40 Wistar rats, half of which were male and subjected to the HFD or Chow diets. Several tasks were employed to assess behavior, including the Variable Delay to Signal (VDS), the Five Choice Serial Reaction Time Task (5-CSRTT), the Delay Discounting Task (DDT), and the Rodent Gambling Task (rGT). Genetic analyses were performed on the frontal cortex, and metabolomics and fatty acid profiles were examined using stool samples collected on PND298. Results The study revealed that rats exposed to the HFD exhibited heightened impulsivity in the VDS and in the 5-CSRTT, suggesting an increase in motor impulsivity. Notably, no significant effect was observed in the DDT. Surprisingly, the HFD-exposed group demonstrated reduced levels of impulsive-like behaviors, and a different decision making, in the rGT. Furthermore, abnormal gene regultation linked to brain plasticity and dopamine were identified in the frontal cortex. Metabolomics analysis of stool samples, collected in adulthood, indicated lower levels of fatty acids. Discussion These results suggest that HFD exposure during adolescence may create a lasting vulnerability to inhibitory control deficits, specifically in terms of motor impulsivity, and in gene expression as well as in metabolomics profile. ### Competing Interest Statement The authors have declared no competing interest.