Time-response studies on development of cognitive deficits in an experimental model of insulin resistance.
Cognitive deficits
Fructose feeding
Insulin resistance
Metabolic syndrome
Neuroinflammation
Journal
Clinical nutrition (Edinburgh, Scotland)
ISSN: 1532-1983
Titre abrégé: Clin Nutr
Pays: England
ID NLM: 8309603
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
22
08
2017
revised:
30
05
2018
accepted:
19
06
2018
pubmed:
25
7
2018
medline:
2
6
2020
entrez:
25
7
2018
Statut:
ppublish
Résumé
Alzheimer's disease is suggested to be primarily metabolic, mainly characterized by brain insulin resistance. Chronic fructose feeding results in hippocampal insulin resistance. However, variable opinion exists regarding the concentration and duration of fructose feeding to trigger insulin resistance and resultant cognitive insults. Therefore this study was planned to construct a time-response curve of the appearance of fructose-induced insulin resistance and memory insufficiencies in rats over a period of 24 weeks. Further, Pearson's correlations were drawn between indices of insulin resistance and markers of memory deficits at various time points. Male Wistar rats (6 weeks old; 155 ± 5 g) were fed with 15% fructose in normal drinking water for a period of 24 weeks. Body weight, food and water intake were weekly monitored. Fasting blood glucose, glycosylated hemoglobin (HbA Most of the parameters including insulin resistance became evident at the 7th week and continued until the end of study (24th week) whereas cognitive insufficiency became significantly distinct at the 20th, 22nd and 24th week. Significantly increased serum nitro-oxidative stress, inflammatory cytokines and serum homocysteine levels were intensely connected with fructose-induced neuronal deficits. The construction of time response study reveals that the hallmark characteristics of insulin resistance appear from the 7th week of fructose feeding whereas the cognitive dysfunction appears on the 20th week and both persist till the end of the study. Fructose-induced oxidative stress and neuroinflammation plausibly impair neuronal signaling and synaptic plasticity.
Sections du résumé
BACKGROUND & AIMS
Alzheimer's disease is suggested to be primarily metabolic, mainly characterized by brain insulin resistance. Chronic fructose feeding results in hippocampal insulin resistance. However, variable opinion exists regarding the concentration and duration of fructose feeding to trigger insulin resistance and resultant cognitive insults. Therefore this study was planned to construct a time-response curve of the appearance of fructose-induced insulin resistance and memory insufficiencies in rats over a period of 24 weeks. Further, Pearson's correlations were drawn between indices of insulin resistance and markers of memory deficits at various time points.
METHODS
Male Wistar rats (6 weeks old; 155 ± 5 g) were fed with 15% fructose in normal drinking water for a period of 24 weeks. Body weight, food and water intake were weekly monitored. Fasting blood glucose, glycosylated hemoglobin (HbA
RESULTS
Most of the parameters including insulin resistance became evident at the 7th week and continued until the end of study (24th week) whereas cognitive insufficiency became significantly distinct at the 20th, 22nd and 24th week. Significantly increased serum nitro-oxidative stress, inflammatory cytokines and serum homocysteine levels were intensely connected with fructose-induced neuronal deficits.
CONCLUSIONS
The construction of time response study reveals that the hallmark characteristics of insulin resistance appear from the 7th week of fructose feeding whereas the cognitive dysfunction appears on the 20th week and both persist till the end of the study. Fructose-induced oxidative stress and neuroinflammation plausibly impair neuronal signaling and synaptic plasticity.
Identifiants
pubmed: 30037709
pii: S0261-5614(18)31185-3
doi: 10.1016/j.clnu.2018.06.966
pii:
doi:
Substances chimiques
Biomarkers
0
Blood Glucose
0
Cytokines
0
Insulin
0
Homocysteine
0LVT1QZ0BA
Fructose
30237-26-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1447-1456Informations de copyright
Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.