Impaired Brain Cells Response in Obesity


Zara Latif, Fiona E Harrison, Ph.D


Obesity is an epidemic that affects more than one third of the U.S. adult population. The link between obesity and Alzheimer's disease has been firmly established in multiple studies. Obesity contributes to cognitive decline and a state of widespread inflammation that activates immune cells in the body. Neuroinflammation is a result of obesity and is believed to be linked to the pathogenesis of Alzheimer's disease. Microglia serve as the resident macrophages in the brain. They can be activated by a number of inflammatory factors including obesity and Alzheimer's disease pathological changes. The morphology of activated microglia is distinct, activation causes microglial processes to be retracted and causes the soma to increase in size. The effects of obesity on microglial activation are poorly understood particularly in the context of neurodegenerative diseases


In this study, GFP tagged microglia were isolated from brains of CX3CR1 adult mice fed either high fat or low fat diet. Percoll gradient centrifugation was used to isolate the microglia. The cells were then activated in culture using lipopolysaccharides (LPS) and imaged at 2, 6, 10 minutes post treatment. The soma area, process length, and number of processes were compared between groups using ImageJ.


High fat diet microglia exhibit a delayed response to LPS compared to low fat diet cells. The soma area of low fat diet microglia is significantly bigger after 2 minutes of activation (p< 0.05).The same increase was not observed in high fat diet microglia. Similarly process retraction was slower in high fat diet mice at 2 minutes and 6 minutes of activation (p< 0.01).


The data suggest that microglia isolated from high fat diet mice display an altered state of responsiveness compared to low fat diet mice likely due to chronic inflammation as a result of obesity. The inflammatory triggers due to obesity could hinder the microglial ability to efficiently respond to insults from the surrounding microenvironment e.g. Amyloid.

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