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

Overview

Journal Diabetes

Specialty Endocrinology

Date 2012 Dec 20

PMID 23250356

Citations 46

Authors

Antoine Leboucher

Cyril Laurent

Francisco-Jose Fernandez-Gomez

Sylvie Burnouf

Laetitia Troquier

Sabiha Eddarkaoui

Dominique Demeyer

Raphaelle Caillierez

Nadege Zommer

Emmanuelle Vallez

Kadiombo Bantubungi

Christophe Breton

Pascal Pigny

Valerie Buee-Scherrer

Bart Staels

Malika Hamdane

Anne Tailleux

Luc Buee

David Blum

Affiliations

Soon will be listed here.

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.

Citing Articles

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