Short-term high-fat-and-fructose feeding produces insulin signaling alterations accompanied by neurite and synaptic reduction and astroglial activation in the rat hippocampus

J Cereb Blood Flow Metab. 2014 Jun;34(6):1001-8. doi: 10.1038/jcbfm.2014.48. Epub 2014 Mar 26.


Chronic consumption of high-fat-and-fructose diets (HFFD) is associated with the development of insulin resistance (InsRes) and obesity. Systemic insulin resistance resulting from long-term HFFD feeding has detrimental consequences on cognitive performance, neurogenesis, and long-term potentiation establishment, accompanied by neuronal alterations in the hippocampus. However, diet-induced hippocampal InsRes has not been reported. Therefore, we investigated whether short-term HFFD feeding produced hippocampal insulin signaling alterations associated with neuronal changes in the hippocampus. Rats were fed with a control diet or an HFFD consisting of 10% lard supplemented chow and 20% high-fructose syrup in the drinking water. Our results show that 7 days of HFFD feeding induce obesity and InsRes, associated with the following alterations in the hippocampus: (1) a decreased insulin signaling; (2) a decreased hippocampal weight; (3) a reduction in dendritic arborization in CA1 and microtubule-associated protein 2 (MAP-2) levels; (4) a decreased dendritic spine number in CA1 and synaptophysin content, along with an increase in tau phosphorylation; and finally, (5) an increase in reactive astrocyte associated with microglial changes. To our knowledge, this is the first report addressing hippocampal insulin signaling, as well as morphologic, structural, and functional modifications due to short-term HFFD feeding in the rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • Dietary Fats / adverse effects*
  • Dietary Fats / pharmacokinetics
  • Fructose / adverse effects*
  • Fructose / pharmacology
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Insulin / metabolism*
  • Insulin Resistance*
  • Male
  • Neurites / metabolism*
  • Neurites / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*
  • Sweetening Agents / adverse effects*
  • Sweetening Agents / pharmacology
  • Synapses / metabolism*
  • Synapses / pathology


  • Dietary Fats
  • Insulin
  • Sweetening Agents
  • Fructose