Alterations of PI3K and Akt signaling pathways in the hippocampus and hypothalamus of Wistar rats treated with highly palatable food

Nutr Neurosci. 2012 Jan;15(1):10-7. doi: 10.1179/1476830511Y.0000000030.


Background/objectives: Highly palatable food (HPF), which is enriched in simple sugars and saturated fat, contributes to obesity and insulin resistance in humans. These metabolic changes are associated with serious complications of the central nervous system, including an elevated risk of cognitive dysfunction. We, herein, treated rats with HPF and then examined the insulin-signaling pathway, in particular, the levels of phosphatidylinositol-3 kinase (PI3K), Akt, and insulin receptor substrate-1 (IRS-1) in the hippocampus and hypothalamus.

Methods: Adult Wistar rats fed with HPF (heated or not during preparation) for 4 months and then measured the levels of PI3K, Akt, and IRS-1 in the hippocampus and hypothalamus, by western blotting and quantitative real-time polymerase chain reaction.

Results: We observed changes in body weight, glucose intolerance, and lipidemia, confirming that peripheral metabolic alterations were induced using this model. Hippocampal PI3K and hypothalamic Akt were affected in rats that are submitted to chronic exposure to an HPF diet. Moreover, heated HPF caused differentiated alterations in the regulatory subunit of PI3K in the hippocampus.

Discussion: Our data suggest that this diet alters insulin signaling differentially in each brain region, and that hippocampal changes induced by this diet could contribute to the understanding of cognitive impairments that are dependent on the hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Cognition Disorders / metabolism
  • Cognition Disorders / pathology
  • Diet
  • Hippocampus / metabolism*
  • Hypothalamus / metabolism*
  • Insulin / blood
  • Insulin Receptor Substrate Proteins / genetics*
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin Resistance
  • Male
  • Obesity / metabolism
  • Phosphatidylinositol 3-Kinase / genetics*
  • Phosphatidylinositol 3-Kinase / metabolism
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction*


  • Insulin
  • Insulin Receptor Substrate Proteins
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt