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

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.