Neuroinflammation In Non-Alcoholic Fatty Liver Diseased Mice

Non-Alcoholic fatty liver disease (NAFLD) is the term used to describe excessive fat build-up in the liver and can lead to liver damage. It currently affects about one-third of the world\u27s population and 30% of United States citizens. Previous studies have shown that NAFLD induces signs of Alzheimer\u27s disease, indicating that there is a link between NAFLD and neuroinflammation. Our objective is to identify that link and study the role of inflammasomes in NAFLD mediated neuroinflammation. To do this, we fed mice a Methionine-Choline deficient (MCD) diet and ran several gene expression studies using Real-Time PCR targeting Interleukin 6, 18, 1β , Caspase 1, and Matrix Metallopeptidase P9. We then ran an immunofluorescent study targeting ASC2, CASP1, and NLRP3. Finally, we conducted a Western Blot Experiment. Our results showed significantly elevated levels of IL6, IL18, CASP1, MMP9, and IL 1β within MCD-diet mice compared to chow-fed mice. Within the frontal cortex of MCD-diet mice, ASC2, CASP1, and NLRP3 have higher levels of colocalization, meaning more inflammasomes are being activated within the MCD-diet tissues than the chow-diet tissues. Finally, the western blot showed a much higher concentration of High Mobility Box 1 protein (HMGB1) within the MCD-diet samples compared to the chow diet, meaning HMGB1 could be the Damage Associated Molecular Pattern (DAMP) that links NAFLD to neuroinflammation. However, there is not enough solid evidence to provide a definite conclusion and studies are still ongoing