A high-sucrose diet aggravates Alzheimer's disease pathology, attenuates hypothalamic leptin signaling, and impairs food-anticipatory activity in APPswe/PS1dE9 mice.
Alzheimer Disease
/ etiology
Amyloid beta-Peptides
/ metabolism
Animals
Anticipation, Psychological
/ drug effects
Diet, Carbohydrate Loading
/ adverse effects
Eating
/ psychology
Hypothalamus
/ metabolism
Inflammation
Leptin
/ metabolism
Mice, Transgenic
STAT3 Transcription Factor
/ metabolism
Signal Transduction
/ drug effects
Sucrose
/ adverse effects
Alzheimer's disease
High-sucrose diet
Hypothalamus
Leptin
Signal transducer and activator of transcription 3, STAT3
amyloid-β
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
03
04
2019
revised:
19
11
2019
accepted:
22
11
2019
pubmed:
28
12
2019
medline:
30
10
2020
entrez:
28
12
2019
Statut:
ppublish
Résumé
High-fat and high-sugar diets contribute to the prevalence of type 2 diabetes and Alzheimer's disease (AD). Although the impact of high-fat diets on AD pathogenesis has been established, the effect of high-sucrose diets (HSDs) on AD pathogenesis remains unclear. This study sought to determine the impact of HSDs on AD-related pathologies. Male APPswe/PS1dE9 (APP/PS1) transgenic and wild-type mice were provided with HSD and their cognitive and hypothalamus-related noncognitive parameters, including feeding behaviors and glycemic regulation, were compared. HSD-fed APP/PS1 mice showed increased neuroinflammation, as well as increased cortical and serum levels of amyloid-β. HSD-fed APP/PS1 mice showed aggravated obesity, hyperinsulinemia, insulin resistance, and leptin resistance, but there was no induction of hyperphagia or hyperleptinemia. Leptin-induced phosphorylation of signal transducer and activator of transcription 3 in the dorsomedial and ventromedial hypothalamus was reduced in HSD-fed APP/PS1 mice, which might be associated with attenuated food-anticipatory activity, glycemic dysregulation, and AD-related noncognitive symptoms. Our study demonstrates that HSD aggravates metabolic stresses, increases AD-related pathologies, and attenuates hypothalamic leptin signaling in APP/PS1 mice.
Identifiants
pubmed: 31879131
pii: S0197-4580(19)30426-9
doi: 10.1016/j.neurobiolaging.2019.11.018
pii:
doi:
Substances chimiques
Amyloid beta-Peptides
0
Leptin
0
STAT3 Transcription Factor
0
Stat3 protein, mouse
0
Sucrose
57-50-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
60-74Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.