Cognitive resilience despite metabolic dysfunction after adolescent-onset high-fat high-sucrose diet exposure in rats
Adolescence is a sensitive period during which unhealthy diets may shape metabolic health and cognition. Diets high in fat and sugar have been linked to obesity, impaired glucose regulation and hippocampus-dependent deficits, but the exposure duration required to affect cognition remains unclear. This study examined whether adolescent-onset exposure to a high-fat high-sucrose (HFHS) diet induces metabolic dysfunction and impairs object-based memory, spatial working memory and spatial pattern separation in male Long Evans rats. Rats were assigned to a control or HFHS diet at four weeks of age and remained on this diet into adulthood. Basal blood glucose was assessed monthly and home-cage behaviour using 48-hour LABORAS recordings. Cognitive testing started after 10 weeks of diet exposure, when basal glucose was elevated in HFHS-fed rats. Object displacement and novel object recognition were used in short open-field test settings, whereas touchscreen-based trial-unique nonmatching-to-location testing (TUNL) assessed spatial working memory and pattern separation across repeated operant sessions. Finally, glucose (in)tolerance and tissue weights were measured. HFHS diet exposure produced a metabolic phenotype, including increased body weight, elevated basal glucose, impaired glucose tolerance and increased liver and gonadal white adipose tissue weights. The diet also altered the general behavioural repertoire, with increased immobility and grooming and reduced rearing. HFHS-fed rats did not differ from controls in object displacement or novel object recognition performance. In the touchscreen task, both groups acquired the task at a comparable rate. Long-delay and spatial separation challenges reduced performance as expected, confirming task sensitivity, but did not reveal diet-related impairments. These findings show that adolescent-onset HFHS diet exposure induces metabolic dysfunction but does not necessarily produce detectable cognitive impairment when behavioural testing starts after 10 weeks of exposure. Longer exposure or advanced diet-induced inflammatory or neurobiological alterations may be required to reveal cognitive consequences.