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

Abstract

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 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, though overt diabetes did not develop, nor was spatial learning and memory altered. Hippocampal adiponectin levels were reduced in aging animals but 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.

High-fat diet and aging interact to produce neuroinflammation and impair hippocampal- and amygdalar-dependent memory

“…In this study, 14 month old F344 rats that were fed a 36% fat diet supplemented with 10% coconut oil and 2% cholesterol for 6 months were impaired on a water radial arm maze working memory task (Ledreux, et al, 2016). Other aging studies, however, have failed to detect hippocampal-dependent memory impairments caused by HFD consumption (Kesby, et al, 2015, Pancani, et al, 2013). In one of these studies, 14 month-old C57BL/6N mice were fed a 60% fat diet for 3 months, and did not exhibit impaired object or place recognition memory above and beyond that exhibited by chow-fed aging mice (Kesby, et al, 2015).…”

“…In one of these studies, 14 month-old C57BL/6N mice were fed a 60% fat diet for 3 months, and did not exhibit impaired object or place recognition memory above and beyond that exhibited by chow-fed aging mice (Kesby, et al, 2015). In the other study, 13 month-old F344 rats were fed a 42% fat diet for 4.5 months and did not exhibit spatial memory impairments in the Morris water maze (Pancani, et al, 2013). Although it is difficult to pinpoint the exact reasons for the discrepancy between these and our findings, it is likely due to differences in the composition of the diets, the consumption duration, the strain and species of animals used, the exact behavioral parameters used (e.g.…”

Novel calcium-related targets of insulin in hippocampal neurons

“…The rationale for this approach was based on recent evidence from our lab that insulin acutely reduces the calcium-dependent afterhyperpolarization (AHP) in neurons recorded from hippocampal slices (Pancani et al , 2013; Maimaiti et al , 2016). The AHP is a hyperpolarization potential that is enhanced in aging, limits neuronal firing, and is associated with cognitive decline (Disterhoft et al , 1996; Tombaugh et al , 2005; Kadish et al , 2009; Pancani et al , 2013).…”

“…The rationale for this approach was based on recent evidence from our lab that insulin acutely reduces the calcium-dependent afterhyperpolarization (AHP) in neurons recorded from hippocampal slices (Pancani et al , 2013; Maimaiti et al , 2016). The AHP is a hyperpolarization potential that is enhanced in aging, limits neuronal firing, and is associated with cognitive decline (Disterhoft et al , 1996; Tombaugh et al , 2005; Kadish et al , 2009; Pancani et al , 2013). The larger AHP seen in aging, is mediated in part, by an increase in the density of L-VGCCs (Thibault & Landfield, 1996) and by calcium-induced calcium-release (CICR) through activation of ryanodine receptors (RyRs) (Kumar & Foster, 2005; Gant et al , 2006; Gant et al , 2013).…”

Xanthohumol improved cognitive flexibility in young mice

“…Manipulations of fatty acids can affect memory. Mice fed a high fat diet performed much worse in the Morris water maze than control mice [30]. These studies indicate that aging results in perturbed fatty acid metabolism and the presence of increased fat can lead to poorer spatial memory.…”