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

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.

DOI: 10.2337/db12-0866

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@inproceedings{Leboucher2013DetrimentalEO, title={Detrimental Effects of Diet-Induced Obesity on τ Pathology Are Independent of Insulin Resistance in τ Transgenic Mice}, author={Antoine Leboucher and Cyril Laurent and Francisco-Jos{\'e} Fernandez-Gomez and Sylvie Burnouf and Laetitia Troquier and Sabiha Eddarkaoui and Dominique Demeyer and Rapha{\"{e}lle Caillierez and Nad{\`e}ge Zommer and Emmanuelle Vallez and Kadiombo Bantubungi and Christophe Breton and Pascal Pigny and Val{\'e}rie Bu{\'e}e-Scherrer and Bart Staels and Malika Hamdane and Anne Tailleux and Luc Bu{\'e}e and David Blum}, booktitle={Diabetes}, year={2013} }