title: Exercise is more effective than diet control in preventing high fat diet-induced β-amyloid deposition and memory deficit in amyloid precursor protein transgenic mice.
abstract: Accumulating evidence suggests that some dietary patterns, specifically high fat diet (HFD), increase the risk of developing sporadic Alzheimer disease (AD). Thus, interventions targeting HFD-induced metabolic dysfunctions may be effective in preventing the development of AD. We previously demonstrated that amyloid precursor protein (APP)-overexpressing transgenic mice fed HFD showed worsening of cognitive function when compared with control APP mice on normal diet. Moreover, we reported that voluntary exercise ameliorates HFD-induced memory impairment and β-amyloid (Aβ) deposition. In the present study, we conducted diet control to ameliorate the metabolic abnormality caused by HFD on APP transgenic mice and compared the effect of diet control on cognitive function with that of voluntary exercise as well as that of combined (diet control plus exercise) treatment. Surprisingly, we found that exercise was more effective than diet control, although both exercise and diet control ameliorated HFD-induced memory deficit and Aβ deposition. The production of Aβ was not different between the exercise- and the diet control-treated mice. On the other hand, exercise specifically strengthened the activity of neprilysin, the Aβ-degrading enzyme, the level of which was significantly correlated with that of deposited Aβ in our mice. Notably, the effect of the combination treatment (exercise and diet control) on memory and amyloid pathology was not significantly different from that of exercise alone. These studies provide solid evidence that exercise is a useful intervention to rescue HFD-induced aggravation of cognitive decline in transgenic model mice of AD.
authors.affiliation: School of Human Health Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Maesako
authors.forename: Kengo
authors.initials: K
authors.lastname: Uemura
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kubota
authors.forename: Akira
authors.initials: A
authors.lastname: Kuzuya
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sasaki
authors.forename: Naoko
authors.initials: N
authors.lastname: Hayashida
authors.forename: Megumi
authors.initials: M
authors.lastname: Asada-Utsugi
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Watanabe
authors.forename: Maiko
authors.initials: M
authors.lastname: Uemura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kihara
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
authors.forename: Ayae
authors.initials: A
authors.lastname: Kinoshita
mesh_terms: D000544:Alzheimer Disease / Q000178:diet therapy / Q000235:genetics / Q000517:prevention & control*; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D003071:Cognition / Q000502:physiology; D004041:Dietary Fats / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000178:diet therapy / Q000235:genetics; D006946:Hyperinsulinism / Q000178:diet therapy / Q000235:genetics; D008297:Male; D008569:Memory Disorders / Q000178:diet therapy / Q000235:genetics / Q000517:prevention & control*; D008659:Metabolic Diseases / Q000178:diet therapy / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D015260:Neprilysin / Q000378:metabolism; D009765:Obesity / Q000178:diet therapy / Q000235:genetics; D010805:Physical Conditioning, Animal / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D004041:Dietary Fats; D015260:Neprilysin