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Reversal of high fat diet-induced obesity improves glucose tolerance, inflammatory response, β-amyloid accumulation and cognitive decline in the APP/PSEN1 mouse model of Alzheimer's disease.

Citation
Walker, J. M., et al. “Reversal Of High Fat Diet-Induced Obesity Improves Glucose Tolerance, Inflammatory Response, Β-Amyloid Accumulation And Cognitive Decline In The App/Psen1 Mouse Model Of Alzheimer's Disease.”. Neurobiology Of Disease, pp. 87-98.
Center Vanderbilt University
Author Jennifer M Walker, Shilpy Dixit, Anjelica C Saulsberry, James M May, Fiona E Harrison
Keywords Behavior, Cognition, Inflammatory response, β-amyloid, high fat diet, obesity
Abstract

This study assessed the extent to which high fat diet (HFD)-induced β-amyloid accumulation and cognitive decline in APP/PSEN1 mice are reversible through control of fat intake. Ten months of HFD (60% calories from fat) led to significant deficits in a 2-trial Y maze task, and nest building assay, and decreased voluntary locomotor activity. The HFD induced an inflammatory response, indicated by increased expression of several inflammatory markers. Substituting a low fat diet led to pronounced weight loss and correction of glucose intolerance, decreases in the inflammatory response, and improved performance on behavioral tasks in both wild-type and APP/PSEN1 transgenic mice. Insoluble β-amyloid levels, and extent of tau phosphorylation were also lower following dietary reversal in APP/PSEN1 mice compared to high fat-fed animals, indicating that the inflammatory response may have contributed to key pathogenic pathways in the Alzheimer's disease model. The data suggest that weight loss can be a vital strategy for cognitive protection, but also highlight potential mechanisms for intervention when sustained weight loss is not possible.

Year of Publication
2017
Journal
Neurobiology of disease
Volume
100
Number of Pages
87-98
Date Published
04/2017
ISSN Number
1095-953X
DOI
10.1016/j.nbd.2017.01.004
Alternate Journal
Neurobiol. Dis.
PMID
28108292
PMCID
PMC5316363
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