Effect of High Fat High Fructose Diet on Peripheral Immune Cell Trafficking into the Brain in CCR2 Mouse Model

Abstract

Recent studies about the gut‐brain axis suggest that high fat high fructose (HFHF) consumption is associated with chronic peripheral inflammation due to disruption of gut flora. Some evidence suggests that chronic peripheral inflammation may increase blood‐brain barrier (BBB) permeability. This may lead to increase in neuroinflammation and development of neurodegenerative diseases. The current study aims to observe the relationship between HFHF diet and BBB trafficking. We hypothesize that peripheral inflammation induced by HFHF diet will increase BBB permeability allowing for increased peripheral monocyte trafficking to the brain. To test this hypothesis, a mouse with red fluorescent protein (RFP) driven by the chemokine receptor 2 (CCR2), was treated with HFHF or control diet (CD) for five weeks to induce chronic inflammation. CCR2 is expressed on peripheral monocytes and to a lesser degree on microglia in the brain. To differentiate between resident microglia and brain infiltrating peripheral monocytes, tissue sections were stained with CD169, a marker specific for peripheral monocytes. Brain sections from CCR2‐RFP mice were stained by immunofluorescence in the hippocampal areas of CA1, CA3, and the dentate gyrus as these areas are affected in the neurodegenerative Alzheimer's Disease. CD169 and CCR2 stained cells were quantified using mean intensity to determine the effects of diet on infiltrating peripheral monocytes. In CA3, CCR2 CD mice presented with significantly decreased CCR2 and CD169 mean intensity as compared with WT CD mice (p=0.048, p=0.03). This may be because the Tg only has one allele of CCR2, permitting less trafficking than WT mice, which have two alleles. In CA1, there was a main effect of diet such that Tg HFHF treated mice showed a significant decrease in CD169 mean intensity compared to Tg CD (p=0.02). The low number of animals, the old age of the animals, and the time treated with diet may have impacted our findings. The current data did not support our hypothesis that HFHF diet increases peripheral trafficking across the BBB. Future directions include repeating this experiment with more animals, and treating the animals with HFHF diet for a longer period.Support or Funding InformationWork was funded by the NIH NIA RO1 RF1AG051514 (MGT) and the APS IOSP Fellowship.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.