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Review
. 2018 Feb:64:48-53.
doi: 10.1016/j.ijdevneu.2017.03.011. Epub 2017 Mar 31.

Cognitive deficits associated with a high-fat diet and insulin resistance are potentiated by overexpression of ecto-nucleotide pyrophosphatase phosphodiesterase-1

J M Kasper  1 , A J Milton  2 , A E Smith  2 , F Laezza  3 , G Taglialatela  4 , J D Hommel  2 , N Abate  5
Affiliations
Review

Cognitive deficits associated with a high-fat diet and insulin resistance are potentiated by overexpression of ecto-nucleotide pyrophosphatase phosphodiesterase-1

J M Kasper et al. Int J Dev Neurosci. 2018 Feb.

Abstract

There is growing evidence that over consumption of high-fat foods and insulin resistance may alter hippocampal-dependent cognitive function. To study the individual contributions of diet and peripheral insulin resistance to learning and memory, we used a transgenic mouse line that overexpresses ecto-nucleotide pyrophosphatase phosphodiesterase-1 in adipocytes, which inhibits the insulin receptor. Here, we demonstrate that a model of peripheral insulin resistance exacerbates high-fat diet induced deficits in performance on the Morris Water Maze task. This finding was then reviewed in the context of the greater literature to explore potential mechanisms including triglyceride storage, adiponectin, lipid composition, insulin signaling, oxidative stress, and hippocampal signaling. Together, these findings further our understanding of the complex relationship among peripheral insulin resistance, diet and memory.

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Figures

Fig. 1
Fig. 1
Acquisition of Morris water maze visible platform task. Average time to platform (A) and velocity (B) over repeated days is not different between groups. Values are mean ± SEM to find platform in 60 second trials.
Fig. 2
Fig. 2
AtENPP1-Tg exacerbates HFD induced deficits in Morris water maze probe trial performance. (A) Mean ± SEM time in goal quadrant during probe trial. * indicates p < 0.05. (B) Representative traces of mouse locomotion during the third probe trial. Double circle represents the trained location of the platform in the goal quadrant, which was removed for probe trial testing.
Fig. 3
Fig. 3
Weakened hippocampal signaling in At-ENPP1-Tg mice fed a HFD. (A) CA1 extracellular field recordings show depressed signaling in WT mice fed a HFD, which was further augmented in At-ENPP1-Tg mice fed a HFD. Averages of these recordings are represented in (B) at increasing stimulation intensities. * indicates p<0.05, **p<0.01, ***p<0.001 relative to RC WT. Reproduced from Sallam [29] with permission from John Wiley and Sons.
Fig. 4
Fig. 4
Graphical depiction of proposed mechanisms that mediate diet and insulin resistance-induced deficits in cognition.
See this image and copyright information in PMC

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