title: 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.
authors.affiliation: Université Lille-Nord de France, Université du Droit et de Santé de Lille, Lille, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Leboucher
authors.forename: Cyril
authors.initials: C
authors.lastname: Laurent
authors.forename: Francisco-José
authors.initials: FJ
authors.lastname: Fernandez-Gomez
authors.forename: Sylvie
authors.initials: S
authors.lastname: Burnouf
authors.forename: Laetitia
authors.initials: L
authors.lastname: Troquier
authors.forename: Sabiha
authors.initials: S
authors.lastname: Eddarkaoui
authors.forename: Dominique
authors.initials: D
authors.lastname: Demeyer
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Caillierez
authors.forename: Nadège
authors.initials: N
authors.lastname: Zommer
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Vallez
authors.forename: Kadiombo
authors.initials: K
authors.lastname: Bantubungi
authors.forename: Christophe
authors.initials: C
authors.lastname: Breton
authors.forename: Pascal
authors.initials: P
authors.lastname: Pigny
authors.forename: Valérie
authors.initials: V
authors.lastname: Buée-Scherrer
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Malika
authors.initials: M
authors.lastname: Hamdane
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleux
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.forename: David
authors.initials: D
authors.lastname: Blum
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D059305:Diet, High-Fat / Q000009:adverse effects*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D055504:Insulin Receptor Substrate Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D007859:Learning Disabilities / Q000209:etiology; D008297:Male; D008569:Memory Disorders / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011897:Random Allocation; D015398:Signal Transduction; D013037:Spatial Behavior; D024801:Tauopathies / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D009419:Nerve Tissue Proteins; D016875:tau Proteins