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

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.

Amelioration of hippocampal dysfunction by adipose tissue‐targeted stem cell transplantation in a mouse model of type 2 diabetes

“…Water Maze, AtENPP1Tg mice on HFD showed impaired performance as a behavioral correlate for reduced synaptic transmission (Kasper et al, 2018). Building on these results, in the current study, we identified synaptic plasticity deficits in the CA1 area could contribute to the cognitive decrements.…”

“…We tested this hypothesis and observed that adipose tissue dysfunction during HFD intake has detrimental consequences in the cellular learning associated with the hippocampal circuitry required for learning, memory and cognitive function. In a previous study, we observed that in Morris Water Maze, At ENPP1 Tg mice on HFD showed impaired performance as a behavioral correlate for reduced synaptic transmission (Kasper et al, ). Building on these results, in the current study, we identified synaptic plasticity deficits in the CA1 area could contribute to the cognitive decrements.…”

Associations of cord blood leptin and adiponectin with children’s cognitive abilities

“…Adiponectin, an anti-inflammatory cytokine, interacts with the brain by modulating inflammatory responses (Arnoldussen et al, 2014). Decreases in adiponectin may increase pro-inflammatory cytokine concentrations, which could lead to neuroinflammation and subsequent cognitive impairments (Kasper et al, 2017). In rodents, adiponectin is shown to have neuroprotective effects (Nishimura et al, 2008; Jeon et al, 2009; Ng and Chan, 2017).…”

Huperzine A ameliorates obesity-related cognitive performance impairments involving neuronal insulin signaling pathway in mice

“…Insulin signaling has been reported to play an important role in cognitive function [ 39 , 40 ]. To further investigate the changes in insulin signaling after Hup A treatment, we tested the phosphorylation level of Akt at serine 473 (p-Akt), which is a necessary residue for Akt activity [ 41 ].…”