Predicting the effects of a high‐energy diet on fatty liver and hippocampal‐dependent memory in male rats

OBJECTIVE: In rodents, diets exceeding nutritional requirements (i.e., high-energy diets; HED) impair hippocampal-dependent memory. Our research suggests that the effects likely involve HED-induced increases in liver lipids. In this experiment, rats were provided with diet choices to test whether voluntary consumption of a HED impairs spatial memory, whether differences in initial weight gain predict memory deficits, and whether increases in liver lipids are associated with the memory deficits. DESIGN AND METHODS: Adult male Sprague-Dawley rats were given a control diet or cafeteria-style HED for 8 weeks. Weight gain during the first 5 days on the diet was used to divide rats into a HED-Lean group and a HED-Obese group. Spatial water maze memory was tested 8 weeks later and postmortem liver lipid concentrations were quantified. RESULTS: Compared with the HED-Lean and control rats, the HED-Obese rats had impaired spatial memory and met the human diagnostic criterion of non-alcoholic fatty liver disease (>5% liver lipids relative to liver weight). Moreover, liver lipids were correlated with memory deficits. CONCLUSIONS: These findings show that voluntary consumption of a HED impairs memory, that initial weight gain predicts fatty liver and memory deficits, and that fatty liver may contribute to the memory-impairing effects of obesity.