High-fat diet reduces novelty-induced expression of activity-regulated cytoskeleton-associated protein

Tsan Ju Chen*, Shun Sheng Chen, Dean Chuan Wang, Hui Shan Hung

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

11 Scopus citations


Chronic high-fat-diet (HFD) consumption can lead to the development of brain insulin resistance, which then exerts deleterious effects on learning and memory. Activity-regulated cytoskeleton-associated protein (Arc) is a memory-related protein, and its expression can be induced by insulin stimulation. In HFD-fed animals, their basal Arc protein levels in cerebral cortex and hippocampus are reduced. However, the effects of HFD on novelty-induced Arc protein expression that is important for cognitive function is still unknown. In the present study, after feeding HFD (60% kcal from fat) for 5 weeks, mice developed brain insulin resistance and had a significant reduction in the novelty-induced but not the basal Arc protein levels in their hippocampi. Further experiments were performed in primary rat hippocampal neurons. The results show that, under the condition of neuronal insulin resistance, acute insulin stimulation induced less activation of the phosphatidylinositol 3-kinase/protein kinase B/p70 ribosomal S6 kinase (PI3K/Akt/p70S6K) pathway, resulting in reduced induction of Arc protein expression. Accordingly, it is suggested that following HFD feeding, the reduction in novelty-induced Arc protein expression in animal's hippocampus is probably related to a suppressed activation of the PI3K/Akt/p70S6K pathway due to the existence of brain insulin resistance.

Original languageEnglish
Pages (from-to)1065-1075
Number of pages11
JournalJournal of Cellular Physiology
Issue number2
StatePublished - 01 02 2020

Bibliographical note

Publisher Copyright:
© 2019 Wiley Periodicals, Inc.


  • Arc
  • PI3K
  • high-fat diet
  • insulin resistance


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