The impact of different fructose loads on insulin sensitivity, inflammation, and PSA-NCAM-mediated plasticity in the hippocampus of fructose-fed male rats
2015
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Objectives: High fructose diet has been shown to have damaging effects
on the hippocampus, a brain region critical for learning and memory.
Fructose-induced hippocampal dysfunction may arise from insulin
resistance and inflammation, and from concomitant changes in
plasticity-related presynaptic proteins. We hypothesized that long-term
access to fructose (10\% and 60\% solutions over a period of 9 weeks)
affects insulin sensitivity, hippocampal inflammation, and synaptic
plasticity in male Wistar rats.
Methods: We used the area under curve (AUC) glucose value and inhibitory
Ser(307) phosphorylation of hippocampal insulin receptor substrate 1
(IRS-1) as hallmarks of insulin resistance. To examine inflammatory
state, we analysed protein levels and intracellular redistribution of
glucocorticoid receptor and nuclear factor-kappa B (NF kappa B), as well
as mRNA levels of tumour necrosis factor-alpha (TNF-alpha),
interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta). Polysialylated
neural cell adhesion molecule (PSA-NCAM) protein was used as a synaptic
plasticity marker.
Results: The results indicate different impacts of diverse
fructose-enriched diets on insulin sensitivity and hippocampal
inflammation and plasticity. Long-term ingestion of 10\% fructose
solution led to increase in AUC glucose value, as well as to elevation
in hippocampal IRS-1 Ser(307) phosphorylation and increase in IL-6 mRNA.
In rats consuming 60\% fructose, the level of PSA-NCAM was reduced, in
parallel with augmented glucocorticoid signalization.
Discussion: The results showed that long-term consumption of 10\%
fructose solution induces hippocampal insulin resistance and
inflammation, with no concomitant plasticity changes. Interestingly,
rats fed with higher concentrations of fructose displayed impaired
plastic response of the hippocampus, coinciding with augmented
glucocorticoid signalling, which may provide a basis for cognitive
deficits associated with metabolic syndrome.
Кључне речи:
Fructose diet; Hippocampus; Inflammation; Insulin sensitivityИзвор:
Nutritional Neuroscience, 2015, 18, 2, 66-75
DOI: 10.1179/1476830513Y.0000000098
ISSN: 1476-8305