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PLoS One. 2018 Feb 14;13(2):e0191909. doi: 10.1371/journal.pone.0191909. eCollection 2018.

Reduced cognitive function, increased blood-brain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr -/-and C57BL/6 mice fed a western diet.

Author information

1
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, United States of America.
2
Division of Cardiovascular Medicine, Department of Internal Medicine, University of California, Davis, California, United States of America.
3
Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
4
Department of Environmental Toxicology, University of California, Davis, California, United States of America.
5
Magnetic Resonance Research Center, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
6
Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, California, United States of America.
7
Department of Physiology and Membrane Biology, University of California, Davis, California, United States of America.
8
Department of Endocrinology, Yale University, New Haven, Connecticut, United States of America.
9
Yale PET Center, Department of Diagnostic Radiology, Yale University, New Haven, Connecticut, United States of America.
10
West Coast Metabolomics Center, Genome Center, University of California, Davis, California, United States of America.

Abstract

Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze. Also, western diet significantly increased BBB transport, as well as microvessel factor VIII in LDLr -/- and microglia IBA1 staining in WT, both indicators of activation and neuroinflammation. Interestingly, LDLr -/- mice had a significant increase in 18F- fluorodeoxyglucose uptake irrespective of diet and brain 1H-magnetic resonance spectroscopy showed increased lactate and lipid moieties. Metabolic assessments of whole mouse brain by GC/MS and LC/MS/MS showed that a western diet altered brain TCA cycle and β-oxidation intermediates, levels of amino acids, and complex lipid levels and elevated proinflammatory lipid mediators. Our study reveals that the western diet has multiple impacts on brain metabolism, physiology, and altered cognitive function that likely manifest via multiple cellular pathways.

PMID:
29444171
PMCID:
PMC5812615
DOI:
10.1371/journal.pone.0191909
[Indexed for MEDLINE]
Free PMC Article

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