Effect of high-fat diet on metabolic indices, cognition, and neuronal physiology in aging F344 rats.

The prevalence of obesity and type 2 diabetes increases with age. Despite this, few studies have examined these conditions simultaneously in aged animals, and fewer studies have measured the impact of these conditions on brain function. Using an established animal model of brain aging (F344 rats), we investigated whether a high-fat diet (HFD) exacerbates cognitive decline and the hippocampal calcium-dependent afterhyperpolarization (a marker of age-dependent calcium dysregulation). Young and mid-aged animals were maintained on control or HFD for 4.5 months, and peripheral metabolic variables, cognitive function, and electrophysiological responses to insulin in the hippocampus were measured. HFD increased lipid accumulation in the periphery, although overt diabetes did not develop, nor were spatial learning and memory altered. Hippocampal adiponectin levels were reduced in aging animals but were unaffected by HFD. For the first time, however, we show that the AHP is sensitive to insulin, and that this sensitivity is reduced by HFD. Interestingly, although peripheral glucose regulation was relatively insensitive to HFD, the brain appeared to show greater sensitivity to HFD in F344 rats.