Obesogenic diets can produce hippocampal
insulin resistance and impairments to hippocampal-dependent cognition. This study investigated the effect of disrupted
insulin signaling in
Neuropeptide Y (NPY) neurons on diet-induced deficits in hippocampal-dependent memory. Wild-type mice and mice that had a targeted knockout of
insulin receptors on NPY cells (IRlox/lox;NPYCre/+) were given ad libitum access to a high-fat diet (high fat; HF), 10%
sucrose solution (high
sugar; HS), both high-fat diet and
sucrose solution (high fat, high
sugar; HFHS), or a normal fat control chow for 12 weeks. Mice were tested in the Morris Water Maze (MWM), a hippocampal-dependent spatial memory task.
Glucose homeostasis was assessed via a
glucose tolerance test. Independent of genotype, consumption of HF, but not HS, diet increased energy intake,
body weight, and plasma
leptin, and
impaired glucose tolerance. Disrupted
insulin signaling in NPY cells and dietary interventions did not significantly affect the ability of mice to learn the location of the platform in the MWM. However, for IRlox/lox control mice, consumption of HF, but not HS, diet resulted in reduced time spent in the target quadrant during the probe trial, suggesting a hippocampal-dependent
memory deficit. IRlox/lox;NPYCre/+ mice had poor performance in the probe trial regardless of diet, suggesting a floor effect. This study did not find adverse effects of chronic
sucrose intake on metabolic outcomes or hippocampal-dependent memory. These data also suggest that the effects of HF diet on hippocampal-dependent memory may be dependent on
insulin signaling in hippocampal NPY cells.