Effects of short-term Western diet on cerebral oxidative stress and diabetes related factors in APP x PS1 knock-in mice.
A chronic high fat Western diet (WD) promotes a variety of morbidity factors although experimental evidence for short-term WD mediating brain dysfunction remains to be elucidated. The amyloid precursor protein and presenilin-1 (APP x PS1) knock-in mouse model has been demonstrated to recapitulate some key features of Alzheimer's disease pathology, including amyloid-beta (Abeta) pathogenesis. In this study, we placed 1-month-old APP x PS1 mice and non-transgenic littermates on a WD for 4 weeks. The WD resulted in a significant elevation in protein oxidation and lipid peroxidation in the brain of APP x PS1 mice relative to non-transgenic littermates, which occurred in the absence of increased Abeta levels. Altered adipokine levels were also observed in APP x PS1 mice placed on a short-term WD, relative to non-transgenic littermates. Taken together, these data indicate that short-term WD is sufficient to selectively promote cerebral oxidative stress and metabolic disturbances in APP x PS1 knock-in mice, with increased oxidative stress preceding alterations in Abeta. These data have important implications for understanding how WD may potentially contribute to brain dysfunction and the development of neurodegenerative disorders such as Alzheimer's disease.
Studzinski
Christa M
CM
Sanders-Brown Center on Aging, University of Kentucky, Lexington, USA.
Li
Feng
F
Bruce-Keller
Annadora J
AJ
Fernandez-Kim
Sun Ok
SO
Zhang
Le
L
Weidner
Adam M
AM
Markesbery
William R
WR
Murphy
M Paul
MP
Keller
Jeffrey N
JN
D054392:Adipokines / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D048909:Diabetes Complications / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D004041:Dietary Fats / Q000009:adverse effects*; D005260:Female; D005526:Food, Formulated / Q000009:adverse effects*; D055879:Gene Knock-In Techniques; D006801:Humans; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000502:physiology*; D053764:Presenilin-1 / Q000235:genetics
D054392:Adipokines; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004041:Dietary Fats; D053764:Presenilin-1