Detrimental Effects of Diet-Induced Obesity on τ Pathology Is Independent of Insulin Resistance in τ Transgenic Mice

  1. David Blum1,2,6
  1. 1Université Lille-Nord de France, Université du Droit et de la Santé de Lille, Lille, France
  2. 2INSERM U837, Jean-Pierre Aubert Research Centre, Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France
  3. 3INSERM U1011, Lille, France
  4. 4Institut Pasteur de Lille, Lille, France
  5. 5EA 4489, Environnement Perinatal et Croissance, Lille, France
  6. 6Centre Hospitalier Régional Universitaire de Lille, Lille, France
  1. Corresponding author: David Blum, david.blum{at}inserm.fr.

Abstract

The τ pathology found in Alzheimer disease (AD) is crucial in cognitive decline. Midlife development of obesity, a major risk factor of insulin resistance and type 2 diabetes, increases the risk of dementia and AD later in life. The impact of obesity on AD risk has been suggested to be related to central insulin resistance, secondary to peripheral insulin resistance. The effects of diet-induced obesity (DIO) on τ pathology remain unknown. In this study, we evaluated effects of a high-fat diet, given at an early pathological stage, in the THY-Tau22 transgenic mouse model of progressive AD-like τ pathology. We found that early and progressive obesity potentiated spatial learning deficits as well as hippocampal τ pathology at a later stage. Surprisingly, THY-Tau22 mice did not exhibit peripheral insulin resistance. Further, pathological worsening occurred while hippocampal insulin signaling was upregulated. Together, our data demonstrate that DIO worsens τ phosphorylation and learning abilities in τ transgenic mice independently from peripheral/central insulin resistance.

  • Received June 28, 2012.
  • Accepted November 3, 2012.

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