Detrimental Effects of Diet-Induced Obesity on τ Pathology Are Independent of Insulin Resistance in τ Transgenic Mice
- Antoine Leboucher1,2,
- Cyril Laurent1,2,
- Francisco-José Fernandez-Gomez1,2,
- Sylvie Burnouf1,2,
- Laetitia Troquier1,2,
- Sabiha Eddarkaoui1,2,
- Dominique Demeyer1,2,
- Raphaëlle Caillierez1,2,
- Nadège Zommer1,2,
- Emmanuelle Vallez1,3,4,
- Kadiombo Bantubungi1,3,4,
- Christophe Breton1,5,
- Pascal Pigny1,2,6,
- Valérie Buée-Scherrer1,2,
- Bart Staels1,3,4,
- Malika Hamdane1,2,
- Anne Tailleux1,3,4,
- Luc Buée1,2,6 and
- David Blum1,2,6⇑
- 1Université Lille-Nord de France, Université du Droit et de la Santé de Lille, Lille, France
- 2INSERM U837, Jean-Pierre Aubert Research Centre, Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France
- 3INSERM U1011, Lille, France
- 4Institut Pasteur de Lille, Lille, France
- 5EA 4489, Environnement Perinatal et Croissance, Lille, France
- 6Centre Hospitalier Régional Universitaire de Lille, Lille, France
- Corresponding author: David Blum, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db12-0866/-/DC1.
See accompanying commentary, p. 1365.
- Received June 28, 2012.
- Accepted November 3, 2012.
- © 2013 by the American Diabetes Association.
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